US Pat. No. 10,214,725

METHODS AND COMPOSITIONS FOR SOMATIC CELL PROLIFERATION AND VIABILITY

The Regents of The Univer...

1. A method for enhancing proliferation of a neural cell, the method comprising:isolating all heparin binding proteins from a medium conditioned by growth of human embryonic stem cells or human embryonic carcinoma cells, wherein the medium is essentially free of human embryonic stem cells or human embryonic carcinoma cells and wherein the isolating comprises contacting the medium with a solid support conjugated to heparin and eluting the heparin binding proteins bound to the solid support;
contacting the neural cell with a composition comprising all of the heparin binding proteins isolated from the medium conditioned by growth of human embryonic stem cells or human embryonic carcinoma cells,
wherein the contacting is for a period of time sufficient to provide for enhanced proliferation of the neural cell compared to the absence of the heparin binding proteins.

US Pat. No. 10,214,720

LOW RIGIDITY GELS FOR MSC GROWTH MODULATION

Makoto Funaki, Media, PA...

1. A mesenchymal stem cell (MSC)isolated from its biological source,
adhered ex vivo onto the surface of a gel or a gel matrix and in the presence of nutrient material, wherein the surface of said gel or said gel matrix has a rigidity of 250 Pa in the microenvironment of the MSC and comprises adhesion molecules, and
in a quiescent state such that the MSC is arrested in the cell cycle;
wherein said quiescent state is characterized by (i) a lack of proliferation, (ii) a lack of differentiation, (iii) the ability of the MSC to express proteins, and (iv) the ability of the MSC to resume proliferation and differentiation upon exposure to a chemical stimulus, a mechanical stimulus, a physical factor or a combination thereof; and
wherein said MSC exhibits a rounded morphology.

US Pat. No. 10,214,718

DISTRIBUTED PERFUSION BIOREACTOR SYSTEM FOR CONTINUOUS CULTURE OF BIOLOGICAL CELLS

University of Massachuset...

1. A distributed bioreactor system for producing and maintaining a continuous biological cell culture, the system comprising:a nurse perfused bioreactor configured to produce and maintain a cell culture, the nurse perfused bioreactor coupled to a nurse perfusion device;
a plurality of peripheral bioreactors configured to produce and maintain a cell culture in parallel;
an individual and distinct peripheral perfusion device positioned proximal to and coupled to each respective individual and distinct peripheral bioreactor of the plurality of peripheral bioreactors;
one or more control devices coupled to and configured to control the nurse perfusion device and the peripheral perfusion devices;
a multi-way manifold coupled to the nurse perfused bioreactor; and
a plurality of one-way fluid conduits configured to provide fluid communication from the nurse perfused bioreactor to the plurality of peripheral bioreactors, each one-way fluid conduit coupling the nurse perfused bioreactor to one of the peripheral bioreactors using the multi-way manifold;
wherein configuration of the multi-way manifold and the one-way fluid conduits enables transfer of the cell culture from the nurse bioreactor to at least two of the peripheral bioreactors and maintains fluid isolation among each of the peripheral bioreactors.

US Pat. No. 10,214,717

CELL DETERMINATION DEVICE, CELL DETERMINATION METHOD, AND CELL DETERMINATION PROGRAM

FUJIFILM Corporation, To...

1. A cell determination device comprising:a controller configured to
acquire information relating to a proliferation rate of a cell and information relating to a movement distance of the cell per unit time based on a plurality of cell images obtained by imaging the cell in a time series manner,
determine a state of the cell by comparing the information relating to the proliferation rate and the information relating to the movement distance with a threshold value of the proliferation rate and a threshold value of the movement distance respectively, and
acquire information relating to a culture period of the cell,
wherein the controller changes the threshold value of the proliferation rate and the threshold value of the movement distance that are used for the comparison according to the information relating to the culture period.

US Pat. No. 10,214,716

METHOD AND APPARATUS FOR CONTINUOUS AUTOMATED PERFUSION SYSTEM HARVESTING FROM IN-SITU FILTRATION PROBE

Flownamics Analytical Ins...

1. A method for monitoring flow, the method comprising:setting an interval during which a pump is run to introduce a flow of sterile media into a reactor;
running the pump to introduce the flow of sterile media into the reactor;
introducing an amount of air into the flow of sterile media flowing into the reactor;
sensing, with a first sensor, a first time when a lead line of the flow of sterile media following the amount of air reaches the first sensor;
sensing, with a second sensor, a second time when the lead line of the flow of sterile media reaches the second sensor;
using the first time and the second time to determine a flow rate for the flow of sterile media; and
adjusting the interval during which the pump is run based on the determined flow rate for the flow of sterile media.

US Pat. No. 10,214,715

BIOREACTOR SYSTEM FOR STEM CELL EXPANSION

Synthecon, Inc., Houston...

11. A bioreactor chamber comprising:(a) a cylindrical sleeve with a hollow core;
(b) an inlet cap mounted on a first end of the sleeve having an inlet nozzle centrally mounted on an exterior surface of the inlet cap, wherein a through bore of the inlet nozzle passes through the inlet cap to the hollow core of the sleeve;
(c) an outlet cap mounted on a second end of the sleeve having an outlet nozzle centrally mounted on an exterior surface of the outlet cap, wherein a through bore of the outlet nozzle passes through the outlet cap to the hollow core of the sleeve;
(d) a porous perfusion core having a central bore axially aligned with the through bore of the inlet nozzle and the through bore of the outlet nozzle, wherein an impermeable plug is positioned within the central bore dividing the central bore into a first inlet segment and a second outlet segment; and
(e) a plurality of porous scaffold disks, each disk having at least one protrusion extending outwardly a first distance from a flat surface of the disk and a central aperture, wherein the central apertures of a plurality of scaffolds disks are threaded over an external surface of the perfusion core to align the scaffolds disks along a length of the perfusion core, wherein each disk abuts the protrusions of an adjacent disk to form a media channel between adjacent disks having a width substantially equal to the first distance.

US Pat. No. 10,214,714

PERFUSION BIOREACTOR

New York Stem Cell Founda...

1. A perfusion bioreactor suitable for use in the preparation of a tissue graft segment comprising:a) a graft chamber comprising a graft chamber floor;
b) an equilibration chamber adjacent the graft chamber and in fluid communication with the graft chamber, wherein the equilibration chamber comprises an equilibration chamber floor having a fluid opening opposing the graft chamber and in fluid communication with an inlet; and
c) an outlet disposed downstream of the graft chamber and the equilibration chamber, wherein a fluid path is defined between the inlet and the outlet whereby fluid flows through the graft chamber and the equilibration chamber from the fluid opening to the outlet, and wherein the bioreactor is configured such that fluid enters into the equilibration chamber generally perpendicular to the equilibration chamber floor and the graft chamber floor.

US Pat. No. 10,214,713

APPARATUSES AND METHODS FOR HIGH-THROUGHPUT PROTEIN SYNTHESIS

UNIVERSITY OF FLORIDA RES...

1. An apparatus comprising a plurality of devices for cell-free protein synthesis, each of the devices comprising:a) a reaction chamber,
b) at least two feeding chambers, and
c) at least two porous membranes separating the reaction chamber and the at least two feeding chambers, wherein (1) the at least two porous membranes allow passage of certain chemicals between the reaction chamber and the at least two feeding chambers while preventing passage of other chemicals from the reaction chamber and the at least two feeding chambers, and (2) the at least two porous membranes are in substantially vertical position.

US Pat. No. 10,214,712

APPARATUS FOR RECEIVING AND CONDITIONING ORGANIC WASTE BY ANAEROBIC BIOCONVERSION

1. An apparatus for receiving and treating organic waste by anaerobic bioconversion comprising a closed tank (1) which constitutes a bioconversion site, provided in an upper part of the closed tank with a device (4) for storing and pressurizing biogas produced, the closed tank (1) comprising a main enclosure that surrounds an internal and central secondary enclosure which the internal and secondary enclosure is surmounted by a liquid-solid phase separator (2.2),characterized in that:
the internal and central secondary enclosure is a gizzard (2) comprising a cylindrical gizzard body mounted removably along a central axis of the closed tank (1), the cylindrical gizzard body (2) constituting a rotational bearing coupled to a rotatable mechanical stirrer (2.3),
the gizzard (2) forms a sub-assembly with, or is removably connected to, a circulation and distribution unit (3) arranged to control flux of substrate inside the closed tank (1) of the apparatus,
said device (4) for storing and pressurizing biogas produced is a gasometric dome (4) mounted for axial displacement and configured to rotate with the rotatable mechanical stirrer (2.3), driven in rotation by a motorisation device (5.41,5.42) that does not interfere with the axial displacement of the gasometric dome (4), the rotatable mechanical stirrer (2.3) being arranged and configured to agitate a fermentative environment contained in the main enclosure of the closed tank (1), and
the gasometric dome (4) is configured to be retractable or at least partly retractable to provide access to internal parts of the apparatus and to allow the gizzard (2) to be removed from the apparatus.

US Pat. No. 10,214,711

FRACTIONATION OF HOP OILS USING LIQUID AND SUPERCRITICAL CARBON DIOXIDE

TOTALLY NATURAL SOLUTIONS...

1. A method for extracting two or more fractions from hop oil, said method comprising the steps of:a) providing an inert adsorbing support;
b) after step a), loading the hop oil onto the support of step a) at a loading rate ranging between 1 and 70 mass %;
c) after step b), separating a first fraction with liquid carbon dioxide at a first temperature ranging between 0° C. and 30° C. and a first pressure ranging between 40 bars and 72.8 bars and a first flow rate ranging between 1 g and 400 g/kg supported material/min;
d) after step c), separating a second fraction with supercritical carbon dioxide at a second temperature ranging between 31° C. and 80° C. and a second pressure of at least 72.8 bars, and a second flow rate ranging between 1 g and 400 g/kg supported material/min;
e) after step d), separating a further fraction or a new fraction with supercritical carbon dioxide at a temperature of at least 31° C. and a pressure of at least 72.8 bars and a flow rate ranging between 1 g and 400 g/kg supported material/min using a co-solvent at a level ranging between 0.05 vol % and 100 vol % of the CO2 flowrate;
f) soaking the support resulting from step e) into a solvent selected from a group consisting of water, ethanol, and carbon dioxide obtained from biological and sustainable sources; and
g) decanting or filtering the solvent from the support and subsequently evaporating or distilling said solvent.

US Pat. No. 10,214,710

INTERCALATED BLEACH COMPOSITIONS, RELATED METHODS OF MANUFACTURE AND USE

The Clorox Company, Oakl...

1. A composition comprising:a bleach compound having the formula:
Mx(OCl)y(O)m(OH)n
wherein M is at least one of magnesium or calcium and optionally, at least one additional alkaline earth metal;
wherein x and y independently are any number greater than or equal to 1;
wherein m and n independently are any number greater than or equal to 0, but m and n are not both 0;
wherein x is ?3y; and
wherein the composition may be embedded or integrated into a plastic film.

US Pat. No. 10,214,707

AUTOMATIC DISHWASHING DETERGENT COMPOSITION

1. An automatic dishwashing detergent composition having a pH as measured in 1% weight aqueous solution at 25° C. of from about 5 to about 7.5, the composition comprising an esterified alkyl alkoxylated surfactant of general formula (I)
wherein
R is a branched or unbranched alkyl radical having 8 to 16 carbon atoms;
R3, R1 independently of one another, are hydrogen or a branched or unbranched alkyl radical having 1 to 5 carbon atoms;
R2 is an unbranched alkyl radical having 5 to 17 carbon atoms;
l, n independently of one another, are a number from 1 to 5 and
m is a number from 13 to 35;
wherein the composition further comprises an alkoxylated polyalkyleneimine.

US Pat. No. 10,214,706

FRAGRANCE CARRIER

1. A fragrance mixture comprising:a fragrance carrier comprising 1,2,3-triacetoxypropane (triacetin) of formula I:

a Polyamide-3, wherein the 1,2,3-triacetoxypropane and the Polyamide-3 are added together at a 1:1 ratio v/v to form the fragrance mixture configured to melt in a temperature range of 67° C. to 70° C. and wherein the fragrance mixture configured to incorporate an essential oil fragrance at a 1:1 ratio v/v.

US Pat. No. 10,214,705

METHOD AND DEVICE FOR PROCESSING AN ORGANIC OIL IN STEPS

GEA Westfalia Separator G...

1. A method for stepwise processing of an organic oil, the method comprising the steps of:A providing a raw oil;
B degumming the raw oil by adding water and/or acid to the raw oil and forming at least two phases, an aqueous phase and an oil phase, and separating the aqueous phase enriched is phospholipid from the oil phase;
C adding sodium hydrogencarbonate and/or sodium acetate to the oil phase from step B, and removing alkaline earth metal compounds and/or phospholipids and/or sterylglycosides, in solution or suspension in an aqueous phase, from the oil phase; and
D hydrolyzing free fatty acids by adding an alkaline agent to the oil phase from step C and removing these hydrolyzed fatty acids from the oil phase,
wherein the hydrolyzed fatty acids have less than 3 wt % of organic impurities.

US Pat. No. 10,214,704

ANTI-DEGRADATION AND SELF-HEALING LUBRICATING OIL

BAKER HUGHES, A GE COMPAN...

1. A lubricating oil comprising:a base oil; and
an anti-degradation additive comprising nanocapsules having an average particle size of about 1 nm to about 500 nm;
the nanocapsules having a core of a neutralizing material and a polymeric encapsulant configured to release the neutralizing material in an acidic environment,
the encapsulate comprising a pyridine-containing polyurethane, a pyridine-containing polyurea, or a combination comprising at least one of the foregoing, and
the neutralizing material comprising a C10-20 amine, a C10-20 alcohol, or a combination comprising at least one of the foregoing.

US Pat. No. 10,214,701

METHOD AND APPARATUS FOR PROCESSING OF CARBON-CONTAINING FEED STOCK INTO GASIFICATION GAS

Rain Water, LLC, Ramona,...

1. A downdraft gasification apparatus comprising:an elongated external vessel;
an elongated internal vessel, wherein said internal vessel is located inside said external vessel, thereby forming a void between said internal vessel and said external vessel;
a gasifier trunk, which is characterized by an axis and which comprises an inside surface, outside surface, an upper end and a lower end, a plurality of slits positioned substantially along the length of said gasifier trunk, wherein each of said plurality of slits is characterized by an upper slit end and a lower slit end, wherein at least one of said plurality of slits is characterized by a width at said lower slit end that is greater than a width at said upper slit end and wherein said gasifier trunk is further characterized by a cross-section of said lower end perpendicular to said axis and a cross-section of said upper end perpendicular to said axis, wherein said cross-section of said lower end is greater than said cross-section of said upper end;
a loading mechanism, comprising an elongated loading mechanism trunk and a feedstock feeder for moving said feedstock along said elongated loading mechanism trunk, wherein said loading mechanism is positioned so as to enable the feeding of said feedstock into said upper end of said gasifier trunk and down toward said lower end of said gasifier trunk,
a fire chamber, positioned below said lower end of said gasifier trunk, wherein said fire chamber is configured to allow products of said feedstock to enter said fire chamber after passing through said gasifier trunk,
a gas outlet, and
a slag discharge mechanism positioned adjacent to said lower end of said external vessel.

US Pat. No. 10,214,699

SCALE COLLECTION AND PREDISTRIBUTION TRAY FOR VESSEL WITH DOWNWARD TWO-PHASE FLOW

MORTEN MULLER LTD. APS, ...

1. A method for removal of solid contaminants from a process stream comprising a vapor and a liquid and for predistribution of the liquid to a fine distribution tray in a catalytic reactor vessel with concurrent downflow of the vapor and the liquid, the method comprising the steps of:providing a scale collection and predistribution tray inside said catalytic reactor vessel, said scale collection and predistribution tray having a rim;
passing said liquid through a scale collection zone on said scale collection and predistribution tray for settling and deposit of said solid contaminants;
passing said liquid from said scale collection zone towards a weir located at the rim of said scale collection and predistribution tray;
passing said liquid through apertures to said fine distribution tray; and
passing said vapor from the space above said scale collection and predistribution tray through a flow area between said scale collection zone and a wall of said vessel and through the flow area between said weir and the wall of said vessel to said fine distribution tray.

US Pat. No. 10,214,698

METHOD OF PROCESSING CRACKED NAPHTHA TO MAKE A LOW-SULFUR NAPHTHA PRODUCT

SHELL OIL COMPANY, Houst...

1. A method of processing a cracked feed to make a low-sulfur naphtha product that may suitably be used as a blending component of low-sulfur gasoline, wherein said method comprises:passing said cracked feed to a first catalytic distillation column that defines a volume having both a thioetherification zone and a hydrogenation zone at a relative location below the thioetherification zone, wherein the thioetherification zone provides for simultaneously reacting mercaptans with diolefins contained in said cracked feed to form sulfides and separating by distillation the reaction products and hydrocarbons, wherein the hydrogenation zone provides for simultaneously reacting thiophenes in said cracked feed with hydrogen to form mercaptans and separating by distillation the reaction products and hydrocarbons, wherein said cracked feed is a full range naphtha comprising hydrocarbons boiling in the range of from C5 (boiling temperature of hydrocarbon molecules having five carbon atoms per molecule) to 260° C. (500° F.), at least one organic sulfur compound, at least one olefin compound, and at least one diolefin compound, and wherein said cracked feed has a total organic sulfur concentration in the range of from about 500 ppm to about 2 wt. % (20,000 ppm), an olefin concentration in the range of from about 30 wt. % to 75 wt. %, a diolefin concentration in the range upwardly to 2 wt. %;
yielding from said first catalytic distillation column a light overhead product and a heavy bottoms product;
passing said heavy bottoms product to a second catalytic distillation column providing for the selective hydrodesulfurization of sulfur compounds contained in said heavy bottoms product;
yielding from said second catalytic distillation column an overhead product containing hydrogen sulfide and a bottoms product containing at least one sulfur compound;
passing said overhead product to a hydrogen sulfide stripper column providing for the removal of hydrogen sulfide from said overhead product and yielding a stripped bottoms product;
passing said stripped bottoms product to a polishing reactor providing for the selective hydrogenation of said at least one sulfur compound to yield a first treated heavy cat naphtha stream;
passing said bottoms product containing said at least one sulfur compound to a bottoms reactor providing for hydrotreatment of said bottoms product to yield a second treated heavy cat naphtha stream; and
passing both said first treated heavy cat naphtha stream and said second treated heavy cat naphtha stream to a naphtha stabilizer column providing for removal of light hydrocarbons from said first treated heavy cat naphtha stream and said second treated heavy cat naphtha stream to yield a stabilized heavy cat naphtha stream suitable for use as a low-sulfur gasoline blending component having a sulfur concentration of less than 25 ppmw.

US Pat. No. 10,214,697

PROCESS FOR REMOVING SULPHUR COMPOUNDS FROM HYDROCARBONS

ULTRACLEAN FUEL PTY LIMIT...

1. A process for reducing the sulphur content of a hydrocarbon material containing sulphur compounds, the process comprising:a) contacting the hydrocarbon material with one or more primary oxidants to provide a primary oxidised hydrocarbon material such that the primary oxidant odxidizes the sulphur compounds to sulphoxide and/or sulphone compounds, wherein the primary oxidant is selected from one or more of the group consisting of N-chloroimide, hypobromous acid, hypochlorous acid, electrolyzed oxidizing water and catalysed and co-catalysed hydrogen peroxide;
c) contacting the primary oxidised hydrocarbon material with an extractant to allow at least a portion of the sulphoxide and/or sulphone compounds to be extracted into the extractant to give a sulphoxide and/or sulphone stream and a low sulphur hydrocarbon stream; and
d) separating the sulphoxide and/or sulphone stream from the low sulphur hydrocarbon stream,
wherein the process further includes a step of contacting the primary oxidised hydrocarbon material with a secondary oxidant to provide a secondary oxidised hydrocarbon material, wherein the secondary oxidant is selected from one or more of the group consisting of hydroxyl radicals, liquid ferrate (iron VI), chlorine dioxide and hyperfluorous acid/polar liquid solvent, such that the secondary oxidant oxidizes sulphur compounds to sulphoxide and/or sulphone compounds.

US Pat. No. 10,214,696

SYSTEM AND METHOD OF REFINING USED OIL

1. A system for treating used oil comprising:a reactor having at least one inlet port for receiving used oil and a solvent into a main body of the reactor, the main body providing an environment for the used oil and the solvent to have a chemical reaction to produce a fluid mixture and at least some waste byproducts, the reactor having at least one fluid outlet for routing the fluid mixture out of the main body and one opening for routing the waste byproducts out of the reactor;
a reservoir connected to the at least one fluid outlet for receiving the fluid mixture, the reservoir having a reservoir main body for providing an environment for the fluid mixture to further dissipate waste byproducts to a bottom layer of the fluid mixture, the reservoir also having an outlet channel for routing a top layer of the fluid mixture outside of the reservoir main body and the reservoir having a reservoir waste outlet channel for routing the dissipated waste byproducts outside the reservoir;
a housing connected to the reservoir outlet channel for receiving the top layer of the fluid mixture, the housing having a top opening and a housing outlet channel;
a heating unit for heating the housing to cause the solvent present in the top layer of the fluid mixture to vaporize and escape through the top opening;
a condensation unit for receiving the vaporized solvent and turning the vaporized solvent to liquid, the condensation unit having an outlet channel for routing the liquid into the main body of the reactor for reuse; and
a storage unit for collecting treated oil;
wherein the housing outlet channel provides a route for any remaining fluid in the housing after the vaporized solvent has escaped to flow out of the housing and into the storage unit.

US Pat. No. 10,214,695

PROCESS FOR RECOVERING HEAT FROM A HYDROCARBON SEPARATION

UOP LLC, Des Plaines, IL...

1. A process for separating hydrocarbons and recovering heat from a stream, the process comprising:separating a feed stream comprising hydrocarbons in a first separation zone into an overhead stream and a bottoms stream, the overhead stream being a vapor stream and the bottom stream being a liquid stream;
passing at least a portion of the overhead stream to a compressor configured to produce a first output stream and a second output stream, wherein the second output stream has a greater pressure than the first output stream;
transferring heat from at least a first portion of the first output stream of the compressor to the first separation zone and then passing the first portion of the first output stream of the compressor to the first separation zone;
passing a second portion of the first output stream of the compressor to a second separation zone;
removing heat from the second output stream of the compressor; and,
passing the second output stream of the compressor to the second separation zone,
wherein the second output stream of the compressor is cooled by contact cooling with the second portion of the first output stream of the compressor, the second separation zone has a pressure higher than a pressure of the overhead stream, and the second separation zone is configured such that any vapor in the second separation zone is from the compressor.

US Pat. No. 10,214,694

CONFIGURATION IN SINGLE-LOOP SYNFUEL GENERATION

Primus Green Energy Inc.,...

1. A process for making fuel from synthesis gas comprising the steps of:a. passing the synthesis gas through a first reactor to convert synthesis gas to methanol and water, which produces the first exit stream;
b. passing the first exit stream through a second reactor to convert methanol to dimethylether, which produces a second exit stream;
c. passing the second exit stream through a third reactor containing a third catalyst for converting methanol and dimethylether to fuel and heavy gasoline, and a fourth catalyst for converting the heavy gasoline to isoparaffins, naphthenes, and less substituted aromatics, which produces a third exit stream; and
d. recycling the unreacted synthesis gas in the third exit stream, wherein no removal or separation of the first, second, or third exit streams are effected during the process.

US Pat. No. 10,214,693

FLAME-RETARDANT VANILLIN-DERIVED SMALL MOLECULES

International Business Ma...

1. A flame-retardant vanillin-derived small molecule with a formula of:
wherein M is a flame-retardant substituent;
wherein FR is a phosphorus-based moiety; and
wherein R is a substituent selected from a group consisting of a phenyl substituent, an allyl substituent, and a thioether substituent.

US Pat. No. 10,214,692

LIQUID-CRYSTALLINE MEDIUM

MERCK PATENT GMBH, Darms...

1. A liquid-crystalline medium comprising:at least one compound of formula I,

in which
R1 and
R1* each, independently of one another, denote an alkyl or alkoxy radical having 1 to 15 C atoms, where, in addition, one or more CH2 groups in these radicals may each optionally be replaced, independently of one another, by —C?C—, —CF2O—, —CH?CH—,
—O—, —CO—O—, —O—CO— in such a way that O atoms are not linked directly to one another, and in which, in addition, one or more H atoms may each optionally be replaced by halogen,Z1 and Z2 each, independently of one another, denote a single bond, —CH2CH2—, —CH?CH—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, —COO—, —OCO—, —C2F4—, —C?C—, —CF?CF—, or —CH?CHCHO—, and
L1-3 each, independently of one another, denote F, Cl, CF3, OCF3 or CHF2; and
at least one compound selected from formulas IIA-13 to IIA-31, IIA-44 to IIA-52, IIB-7 to IIB-10, L-1 to L-11, T-1 to T-12, T-14 to T-21, BC, CR, PH-1, PH-2, BF-1, BF-2, BS-1, BS-2, O-6, P-1 to P-4, Z-1 to Z-9, and B-1a:
whereinalkyl and alkyl* each, independently of one another, denote a straight-chain alkyl radical having 1-6 C atoms,
alkenyl and alkenyl* each, independently of one another, denote a straight-chain alkenyl radical having 2-6 C atoms, and
(O) denotes a single bond or —O—;
whereinR, R1 and R2 each, independently of one another, denote H, an alkyl or alkenyl radical having up to 15 C atoms which is unsubstituted, or monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups in these radicals may each optionally be replaced by —O—, —S—,
—C?C—, —CF2O—, —OCF2—, —OC—O— or —O—CO— in such a way that O atoms are not linked directly to one another,(O) denotes a single bond or —O—,
alkyl denotes an alkyl radical having 1-6 C atoms, and
s denotes 1 or 2;
whereinR denotes a straight-chain alkyl or alkoxy radical having 1-7 C atoms or alkenyl having 2-6 C atoms,
(O) denotes a single bond or —O—,
m=0, 1, 2, 3, 4, 5 or 6, and
n denotes 0, 1, 2, 3 or 4;
whereinRB1, RB2, RCR1, RCR2, R1, R2 each, independently of one another, denote H, an alkyl or alkenyl radical having up to 15 C atoms which is unsubstituted, or monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups in these radicals may each optionally be replaced by —O—, —S—,
—C?C—, —CF2O—, —OCF2—, —OC—O— or —O—CO— in such a way that O atoms are not linked directly to one another,c is 0, 1 or 2, and
d is 1 or 2;
whereinR1 and R2 each, independently of one another, denote H, an alkyl or alkenyl radical having up to 15 C atoms which is unsubstituted, or monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups in these radicals may each optionally be replaced by —O—, —S—,
—C?C—, —CF2O—, —OCF2—, —OC—O— or —O—CO— in such a way that O atoms are not linked directly to one another;whereinR denotes straight-chain alkyl, alkoxy or alkenyl, each having up to 6 C atoms respectively, and
X denotes F, Cl, CF3, OCF3, OCHFCF3 or CCF2CHFCF3;
in whichR denotes H, an alkyl or alkenyl radical having up to 15 C atoms which is unsubstituted, or monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups in these radicals may each optionally be replaced by —O—, —S—,
—C?C—, —CF2O—, —OCF2—, —OC—O— or —O—CO— in such a way that O atoms are not linked directly to one another,(O) denotes a single bond or —O—, and
alkyl denotes an alkyl radical having 1-6 C atoms;
whereinalkyl* denotes an alkyl radical having 1 6 C atoms.

US Pat. No. 10,214,691

LIQUID-CRYSTALLINE MEDIUM

MERCK PATENT GMBH, Darms...

1. A liquid-crystalline medium comprising:at least one compound of formula I,

in which
R1 and
R1* each, independently of one another, denote an alkyl or alkoxy radical having 1 to 15 C atoms, where, in addition, one or more CH2 groups in these radicals are each optionally replaced, independently of one another, by —C?C—, —CF2O—, —CH?CH—,

 —O—, —CO—O—, —O—CO— in such a way that O atoms are not linked directly to one another, and in which, in addition, one or more H atoms are each optionally replaced by halogen,
Z1 and Z2 each, independently of one another, denote a single bond, —CH2CH2—, —CH?CH—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, —COO—, —OCO—, —C2F4—, —C?C—, —CF?CF—, or —CH?CHCHO—, and
L1-3 each, independently of one another, denote F, Cl, CF3, OCF3 or CHF2, and
at least one compound selected from

in which
R2A, R2B and R2C each, independently of one another, denote alkenyl radical having 2 to 6 C atoms which is unsubstituted, monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups in these radicals are each optionally replaced by —O—, —S—,

 —C?C—, CF2O—, —OCF2—, —OC—O— or —O—CO— in such a way that O atoms are not linked directly to one another,
L1-4 each, independently of one another, denote F, Cl, CF3 or CHF2,
Z2 and Z2? each, independently of one another, denote a single bond, —CH2CH2—, —CH?CH—, —CF2O—, —OCF2—, —CH2O—, —OCH2—, —COO—, —OCO—, —C2F4—, —CF?CF—, or—CH?CHCH2O—,
(O) denotes a single bond or —O—,
p denotes 0, 1 or 2,
q denotes 0 or 1, and
v denotes 1 to 6.

US Pat. No. 10,214,690

LIQUID CRYSTAL COMPOSITION AND A LIQUID CRYSTAL DISPLAY INCLUDING THE SAME

SAMSUNG DISPLAY CO., LTD....

1. A liquid crystal composition, comprising a liquid crystal compound represented by Formula 1:
wherein
is selected from
X1 and X2 are each independently selected from fluorine, CF3, or CnH2n+1,
Z is selected from a single bond, a double bond, CF2CF2, OCF2, or CF2O,
R1 is selected from hydrogen, fluorine, CF3, CnH2n+1, or CnH2n+1O,
R2 is selected from hydrogen, fluorine, CF3, CnH2n+1, or OCnH2n+1,
is selected from
X3 and X4 are each independently selected from hydrogen, fluorine, CF3, or CnH2n+1,
m is a natural number selected from 1 or 2, and
n is a natural number selected from 1 to 5.

US Pat. No. 10,214,689

FLUORESCENT MATERIAL AND LIGHT EMITTING DEVICE

NATIONAL INSTITUTE FOR MA...

1. A fluorescent material comprising at least an A element, a M element, a D element, a E element, and an X element,the A element being at least one element selected from the group consisting of Sr, Mg, Ca, and Ba;
the M element being at least one element selected from the group consisting of Eu, Mn, Ce, Pr, Nd, Sm, Tb, Dy, and Yb;
the D element being at least one element selected from the group consisting of Si, Ge, Sn, Ti, Zr, and Hf;
the E element being at least one element selected from the group consisting of Al, B, Ga, In, Sc, Y, and La;
the X element being at least one element selected from the group consisting of O, N, and F; and
a molar ratio of the M element to a sum of the A element and the M element [M/(A+M)] being 0.06 or less.

US Pat. No. 10,214,687

METHOD FOR PRODUCING AND METHOD FOR PROCESSING COMPLEX FLUORIDE PHOSPHOR

SHIN-ETSU CHEMICAL CO., L...

1. A method for producing a red phosphor that is a manganese-activated complex fluoride represented by the formula (1):A2MF6:Mn  (1)
wherein M is one or more tetravalent element selected from the group consisting of silicon, titanium, zirconium, hafnium, germanium and tin, and A is one or more alkali metal selected from the group consisting of lithium, sodium, potassium, rubidium and cesium, and includes at least sodium and/or potassium, the method comprising the steps of:
mixing, as reaction raw materials, a solid of a complex fluoride represented by the formula (2):
A2MF6  (2)
wherein M is one or more tetravalent element selected from the group consisting of silicon, titanium, zirconium, hafnium, germanium and tin, and A is one or more alkali metal selected from the group consisting of lithium, sodium, potassium, rubidium and cesium, and includes at least sodium and/or potassium, and a solid of a manganese compound represented by the formula (3):
A2MnF6  (3)
wherein A is one or more alkali metal selected from the group consisting of lithium, sodium, potassium, rubidium and cesium, and includes at least sodium and/or potassium, and
heating the mixture at a temperature of at least 100° C. and not above 500° C., wherein
the mixture is combined with a solid of a hydrogenfluoride represented by the formula (4):
A1F.nHF  (4)wherein A1 is one or more alkali metal or ammonium selected from the group consisting of sodium, potassium, rubidium and NH4, and n is a number that is at least 0.7 and not more than 4, and heating the mixture.

US Pat. No. 10,214,686

METHODS FOR ENCAPSULATING NANOCRYSTALS AND RESULTING COMPOSITIONS

Nanosys, Inc., Milpitas,...

1. A microsphere comprising:a composition comprising:
luminescent core-shell nanocrystals; and
an inorganic layer covering each of the luminescent core-shell nanocrystals; and
a barrier layer, disposed on the inorganic layer, configured to hermetically seal the composition, wherein the barrier layer consists essentially of SiO2, TiO2, or Al2O3.

US Pat. No. 10,214,685

OPTICAL ELEMENT FOR CORRECTING COLOR BLINDNESS

Nitto Denko Corporation, ...

1. An ocular lens comprising: an optical element comprising a luminescent compound polymerized into a substantially transparent matrix; wherein the lens is configured so that the optical element modifies a color of an object or image viewed through the optical element by a user to thereby allow the user to better distinguish colors.

US Pat. No. 10,214,684

FRICTION REDUCERS AND WELL TREATMENT FLUIDS

BWA WATER ADDITIVES UK LI...

1. A well treatment fluid comprising (a) tri n-butyl n-tetradecyl phosphonium chloride (TTPC) and (b) a polymeric friction reducer, the polymeric friction reducer comprising a copolymer of acrylamide and acrylic acid, wherein the TTPC is provided in an amount such that the well treatment fluid exhibits a reduction in friction relative to the well treatment fluid lacking the TTPC.

US Pat. No. 10,214,683

SYSTEMS AND METHODS FOR PRODUCING HYDROCARBONS FROM HYDROCARBON BEARING ROCK VIA COMBINED TREATMENT OF THE ROCK AND SUBSEQUENT WATERFLOODING

BP Corporation North Amer...

28. A method for recovering hydrocarbons from hydrocarbon bearing rock in a hydrocarbon recovery operation, the method comprising:(a) applying an aqueous solution to the rock, wherein the aqueous solution comprises water, a thermally activated chemical species, and a plurality of nanoparticles, wherein the thermally activated chemical species is urea, a urea derivative, or a carbamate, wherein the thermally activated chemical agent is thermally activated at or above a threshold temperature between 20° and 150° C. and wherein each nanoparticle has an outer surface that is partially water-wet and partially oil-wet;
(b) thermally activating the thermally activated chemical species in the aqueous solution during or after (a) at a temperature equal to or greater than the threshold temperature to produce carbon-dioxide and at least one of ammonia, amine, and alkanolamine within the rock;
(c) forming a gas-in-water foam in the rock with carbon dioxide gas;
(d) reacting the ammonia, amine, or alkanolamine with organic acids in the hydrocarbons to form surfactants in the rock; and
(e) emulsifying the hydrocarbons in the rock with the surfactants to form an oil-in-water emulsion;
(f) increasing a water wettability of the rock in response to the thermally activation in (b); and
(g) flushing the rock with water after (a), (b), (c), (d), (e), and (f).

US Pat. No. 10,214,682

MICRO-PROPPANT FRACTURING FLUID COMPOSITIONS FOR ENHANCING COMPLEX FRACTURE NETWORK PERFORMANCE

HALLIBURTON ENERGY SERVIC...

9. A method comprising:introducing a fracturing fluid into a wellbore, wherein the fracturing fluid comprises:
an aqueous-based carrier fluid,
a viscoelastic surfactant present in the fracturing fluid at a concentration of between about 1% and about 5% by volume and comprises an amphoteric surfactant having the formula:

where R1 is a saturated or unsaturated, linear or branched, hydrocarbon group of from about 17 to about 29 carbon atoms; R2 and R3 are each a straight chain or branched alkyl or hydroxyalkyl group of from 1 to about 6 carbon atoms; R4 is a H, alkyl or hydroxyalkyl group of from 1 to about 4 carbon atoms; k is an integer of from 2-20; m is an integer from 1-20; and n is an integer of from 0-20, and
micro-proppant particulates having a median particle size of less than 150 ?m; and
delivering the micro-proppant particulates into a secondary fracture of the wellbore.

US Pat. No. 10,214,681

METHOD FOR TREATING A SUBTERRANEAN FORMATION

SCHLUMBERGER TECHNOLOGY C...

1. A method for treating a subterranean formation, the method comprising:combining an aqueous fluid, a biomaterial, an enzyme, and a deactivator to form a non-crosslinked treatment fluid; and
introducing the non-crosslinked treatment fluid into the subterranean formation; wherein:
the enzyme degrades the biomaterial; and
the deactivator is an oxygen-containing arene capable of inhibiting the enzyme from degrading the biomaterial,
wherein the deactivator comprises at least one of a naphthol, dimethoxybenzene, trimethoxybenzene, and a structure represented by

wherein:
R7 represents an alkyl group having about 1 to about 5 atoms optionally including one or more heteroatoms, and
R3, R4, R5, and R6 each independently represents a hydrogen atom, a hydroxyl group, an alkyl group, an alkene group, an ester, a carboxylic acid, an alcohol, an aldehyde, a ketone, an aryl, an aryloxy, cycloalkyl, a carbonyl, or an amino group,
wherein the non-crosslinked treatment fluid does not crosslink.

US Pat. No. 10,214,680

STABILITY IMPROVEMENT OF CO2 FOAM FOR ENHANCED OIL RECOVERY APPLICATIONS USING POLYELECTROLYTES AND POLYELECTROLYTE COMPLEX NANOPARTICLES

The University of Kansas,...

1. In a foam including a non-liquid fluid phase and a liquid dispersion phase, the improvement comprising:the foam having a foam quality ranging from 60% to 90% determined as a percentage total foam volume occupied by the non-liquid fluid phase;
the liquid dispersion phase being a dispersion of polyelectrolyte material and surfactant in water,
the polyelectrolyte material and the surfactant being combined in a ratio of surfactant to polyelectrolyte material ranging from 3:1 to 9:1;
the polyelectrolyte material forming nanoparticles by electrostatic interaction of a cationic and an anionic polyelectrolyte,
the nanoparticles being located at lamellae of the liquid dispersion phase in an effective amount to stabilize the foam;
the polyelectrolyte material being present in an amount ranging from 0.1% to 5% of the liquid phase by weight; and
the non-liquid fluid phase being CO2 in a supercritical state.

US Pat. No. 10,214,679

COMPOSITION AND METHOD FOR RECOVERING HYDROCARBON FLUIDS FROM A SUBTERRANEAN RESERVOIR

Ecolab USA Inc., St. Pau...

1. A method of modifying the permeability to water of a subterranean formation, the method comprising:introducing into the subterranean formation a composition comprising crosslinked expandable polymeric microparticles having an unexpanded volume average particle size diameter from about 0.05 to about 2,000 microns,
wherein the microparticles comprise labile internal crosslinks with a crosslinking agent content from about 50 to about 200,000 ppm of at least one labile crosslinker based on a molar ratio of said polymeric microparticles, wherein the labile crosslinks are capable of cleavage at or below neutral pH,
wherein the microparticles comprise from 0 to about 900 ppm of at least one non-labile crosslinker based on a molar ratio of said polymeric microparticles, and
wherein the at least one labile crosslinker is selected from at least one of the following structures 1-11, 13, and 15-26:

US Pat. No. 10,214,676

USE OF CSH-SEED MODIFIED FIBERS IN OIL FIELD APPLICATIONS

BASF SE, Ludwigshafen (D...

1. A method of utilizing fibers in borehole cementing in the development, exploitation and completion of underground mineral oil and natural gas deposits and in wells, comprising:providing reinforcing fibers,
wherein calcium silicate hydrate crystallization seeds are attached to said fibers via linker moieties,
wherein the fibers are selected from polyvinyl alcohol fibers, polyolefin fibers, polysaccharide fibers and mixtures thereof,
wherein the linker moieties comprise one or more functional groups selected from the group consisting of amine, ammonium, amide, nitrate, sulfate, sulfonate, sulfonamide, carboxylate, silanol, phosphate, phosphinate or phosphonate functional groups,
providing a cement slurry incorporating the fibers,
pumping the slurry into a borehole, and
allowing the slurry to harden.

US Pat. No. 10,214,675

SALT-FREE INVERT EMULSION DRILLING FLUIDS AND METHODS OF DRILLING BOREHOLES

Halliburton Energy Servic...

1. A method for drilling in a subterranean formation comprising:providing an invert emulsion drilling fluid comprising:
an oleaginous continuous phase;
an internal phase comprising an alcohol, wherein the alcohol in the internal phase comprises at least about 40% by weight of the internal phase; and
a suspension agent comprising a combination of a hydrophobic amine and an organic acid,
wherein the organic acid is selected from the group consisting of: lactic acid, formic acid, acrylic acid, acetic acid, chloroacetic acid, dichloroacetic acid, trichloroacetic acid, trifluoroacetic acid, propanoic acid, butyric acid, pentanoic acid, hexanoic acid, heptanoic acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, maleic acid, fumaric acid, aspartic acid, citric acid, isocitric acid, aconitic acid, tartaric acid, benzoic acid, p-amino benzoic acid, phthalic acid, terephthalic acid, trimesic acid, and any combination or derivative thereof,
wherein the hydrophobic amine is a 36 carbon fatty dimer diamine with the molecular structure:
and drilling in at least a portion of the subterranean formation with the drilling fluid.

US Pat. No. 10,214,674

WEIGHTED WELL FLUIDS

HALLIBURTON ENERGY SERVIC...

1. An aqueous-based wellbore fluid comprising:(a) an aqueous solvent;
(b) a weighting agent comprising one or more organic cationic tungstate, or molybdate, or silicate salts dissolved in the solvent;
(c) one or more solid weighting agents; and
wherein the one or more organic cationic tungstates, molybdates, and/or silicates is in an amount such that the density of the aqueous-based fluid composition is from about 15 to about 22 lbs/gal.

US Pat. No. 10,214,672

HEAT-STORAGE MATERIAL, AND HEAT-STORAGE MEMBER, STORAGE CONTAINER, TRANSPORTATION/STORAGE CONTAINER, CONSTRUCTION MATERIAL, AND ARCHITECTURAL STRUCTURE USING THE SAME

SHARP KABUSHIKI KAISHA, ...

2. A heat-storage material comprising:a heat-storage substance which reversibly changes between an aqueous solution containing tetrabutylammonium bromide and a clathrate hydrate containing the tetrabutylammonium bromide as a guest molecule;
ammonium alum dodecahydrate which is added to the aqueous solution; and
a poor solvent for the ammonium alum dodecahydrate, which is added to the aqueous solution, wherein
a concentration of the tetrabutylammonium bromide in the aqueous solution is approximately 25 wt % or more and 40 wt % or less, and
a concentration of the ammonium alum dodecahydrate in the aqueous solution is equal to or more than 2 wt %.

US Pat. No. 10,214,670

REFRIGERANT COMPOSITIONS AND METHODS OF USE

TRANE INTERNATIONAL INC.,...

1. A method of reducing flammability of a refrigerant composition in a heating, ventilation, and air conditioning (HVAC) system, comprising:adding R32 refrigerant into the composition;
adding R1234yf refrigerant into the composition; and
adding an amount of R125 refrigerant into the composition, the R125 refrigerant is relatively less flammable than the R32 refrigerant and the R1234yf refrigerant, wherein the amount of R125 refrigerant is 5.5% by weight, 6.5% by weight, 7.5% by weight, or from 10.5% to 20% by weight, and wherein the percentage by weight of the R32 refrigerant and the R1234yf refrigerant respectively ranges from 64.0 to 69.0 and from 25.5 to 28.5.

US Pat. No. 10,214,667

ADHESIVE TAPE FOR PREVENTING ADHESION OF AQUATIC ORGANISMS

NITTO DENKO CORPORATION, ...

1. A pressure-sensitive adhesive tape for preventing adhesion of aquatic organisms comprising an antifouling layer, a base material layer and a pressure-sensitive adhesive layer in this order, wherein the base material layer contains 50% by weight to 100% by weight of an ionomer resin, and wherein the antifouling layer contains an addition-type silicone resin and a polyether-modified silicone oil,wherein the polyether modified silicone oil is represented by formula (1):
wherein, in the formula (1), R each independently represents an alkyl group having from 1 to 3 carbon atoms, R1 represents an alkylene group having from 1 to 4 carbon atoms, R2 represents a hydrogen atom or an alkyl group having from 1 to 15 carbon atoms, R3 is a polyoxyalkylene group represented by —(C2H4O)a—(C3H6O)b—, a is from 1 to 50, b is from 0 to 30, m is 1 to 7,000, and n is from 1 to 50.

US Pat. No. 10,214,666

OPTICALLY CLEAR ADHESIVES FOR DURABLE PLASTIC BONDING

3M Innovative Properties ...

1. An optically clear adhesive comprising:a copolymer of a monomer mixture comprising:
25 to 80 parts by mass of an alkyl (meth)acrylate;
15 to 50 parts by mass of a hydroxyl group-containing monomer;
5 to 25 parts by mass of a macromer having a glass transition temperature (Tg) of 50° C. or higher, wherein the monomers that constitute the main chain of the macromer includes methacrylate monomers, styrene-based monomers or acrylonitrile, and wherein the number molecular weight of the macromer in Dalton is 2000 or higher and 50000 or lower; and
a crosslinkable monomer comprising difunctional (meth)acrylates or polyfunctional (meth)acrylates, wherein when the total quantity of the alkyl (meth)acrylate, the hydroxyl group-containing monomer, and the macromer is 100 parts by mass, the crosslinkable monomer is at a quantity of 0.01 parts by mass or higher and 5 parts by mass or lower,
wherein the copolymer contains substantially no acidic groups, wherein the acid value of the copolymer that contains substantially no acidic groups is 5 mg KOH/g or lower.

US Pat. No. 10,214,664

FLOOR MARKING TAPE

1. A floor marking tape adhered to a floor wherein the floor marking tape establishes a boundary on the floor; the combination comprising:a floor having an uppermost surface; the uppermost surface of the floor configured to support personnel and equipment thereupon;
a floor marking tape having a body that has an upper surface and a lower surface; the lower surface facing the uppermost surface of the floor to which the floor marking tape is adhered such that the body of the floor marking tape is disposed above the uppermost surface of the floor;
the body of the floor marking tape having a longitudinal direction;
the body of the floor marking tape having first and second lateral edge portions disposed in the longitudinal direction; each of the first and second lateral edge portions having an upper surface and a lower surface;
each of the first and second lateral edge portions having a width defined in a direction perpendicular to the longitudinal direction;
the upper surface of each lateral edge portion comprising an extension of the upper surface of the body;
the lower surface of each lateral edge portion being a flat coplanar extension of the lower surface of the body;
the entire body of each lateral edge portion being tapered with the upper surface of the first lateral edge portion extending to the lower surface of the first lateral edge portion and the upper surface of the second lateral edge portion extending to the lower surface of the second lateral edge portion;
each of the first and second lateral edge portions having a maximum height that is less than its width; and
an adhesive securing the lower surface of the body to the uppermost surface of the floor to establish a boundary.

US Pat. No. 10,214,663

CHEMICAL-MECHANICAL POLISHING COMPOSITION COMPRISING ORGANIC/INORGANIC COMPOSITE PARTICLES

ST. LAWRENCE NANOTECHNOLO...

20. A process, comprising:chemical-mechanical polishing a substrate with a composition comprising an amount of composite particles (A1) and water (E) while applying the composition onto the substrate as a continuous stream or in dropwise fashion, wherein each of the composite particles (A1) comprises
(i) a continuous matrix phase comprising an addition polymer of one or more ethylenically unsaturated monomers;
and
(ii) one or more dispersed phases dispersed in the continuous matrix phase and each consisting of a plurality of divided phase domains consisting of inorganic solid material.

US Pat. No. 10,214,662

METHOD OF PRINTING, IMAGE FORMING APPARATUS AND PRINT

Xerox Corporation, Norwa...

1. A multi-pass printing method comprising:passing a substrate through a printer wherein an image is printed onto the substrate;
applying a release fluid on the substrate having the printed image; and
passing a same side of the substrate through the printer to apply a toner layer onto the substrate having a printed image, wherein the release fluid comprises;
a blend of an amino functional silicone fluid and a non-functional silicone fluid wherein the amino silicone functional fluid is represented by:
wherein Q represents —R1—X, wherein R1 represents an alkyl group having from about 1 to about 10 carbons, X represents —NH2 or —NHR2NH2 with R2 having the same description as R1, n is an integer from 1 to 50, m is an integer from 10 to 5,000, wherein the non-functional silicone fluid is represented by:wherein r is an integer from 10 to 5,000, wherein T1 and T2 are methyl (—CH3), or hydroxyl (—OH), wherein an amount of the amino functional silicone fluid is from about 10 weight percent to about 90 weight percent of the release fluid and an amount of the non-functional silicone fluid is from about 10 weight percent to about 90 weight percent of the release fluid, wherein an amount of silanol (Si—OH) is less than 200 ppm in the release fluid.

US Pat. No. 10,214,656

COPPER NANOPARTICLES AND PRODUCTION METHOD FOR SAME, COPPER NANOPARTICLE FLUID DISPERSION, COPPER NANOINK, COPPER NANOPARTICLE PRESERVATION METHOD, AND COPPER NANOPARTICLE SINTERING METHOD

A SCHOOL CORPORATION KANS...

1. Copper nanoparticles each having a central portion comprising a copper single crystal, and a protective layer surrounding the central portion;(1) the copper nanoparticles having an average particle diameter of 10 nm or less;
(2) the protective layer containing at least one member selected from the group consisting, of C3-6 primary alcohols, C3-6 secondary alcohols, and derivatives thereof; and
(3) the protective layer having a boiling point or thermal decomposition point of 150° C. or less;
wherein the at least one member selected from the group consisting of C3-6 primary alcohols C3-6 secondary alcohols, and derivatives thereof has a group represented by the following formula (1) or (2):

wherein in formulas (1) and (2), the asterisk (*) represents a bonding hand.

US Pat. No. 10,214,655

METAL NANOPARTICLE INK DISPERSION

XEROX CORPORATION, Norwa...

1. A metal nanoparticle inkjet ink dispersion made by mixing ingredients comprising:a first solvent being nonpolar and having a boiling point above 160° C. at 1 atmosphere pressure;
a second solvent having a boiling point above 230° C. at 1 atmosphere pressure, the second solvent being a C10 to C18 arylcycloalkane and having a higher boiling point than the first solvent; and
a plurality of metal nanoparticles,
wherein a weight percent of the first solvent is greater than the weight percent of the second solvent in the inkjet ink dispersion.

US Pat. No. 10,214,653

REFRACTORY ARTICLE AND PRODUCTION METHOD THEREOF

COVESTRO DEUTSCHLAND AG, ...

1. A refractory article comprising(1) a core material comprising a composite wood-based structural material
and
(2) a refractory layer covering one or more surfaces of the core material, and
comprising a non-foamed polyisocyanurate resin, wherein:
the non-foamed polyisocyanurate resin comprises the reaction product of a polyisocyanate with an active hydrogen-containing compound, and a flame retardant; in which said active hydrogen-containing compound comprises a polyol having two or more hydroxyl groups, a hydroxyl number of 120 to 2000 mg-KOH/g, a functionality of 2 to 4, and a molecular weight of 50 to 2000; and from 5 to 30 parts by weight of said active hydrogen-containing compound is used per 100 parts by weight of polyisocyanate; and said flame retardant comprises from 10 to 20 parts by weight of aluminum hydroxide and from 5 to 10 parts by weight of red phosphorus, based on 100 parts by weight of said polyisocyanate, wherein the weight ratio of aluminum hydroxide to red phosphorus is from 1:1 to 4:1.

US Pat. No. 10,214,651

PIGMENT/FRIT MIXTURES

MERCK PATENT GMBH, Darms...

1. A pigment/frit mixture, comprising a mixture of a pearlescent pigment and a frit in the form of particles, wherein the proportion of pearlescent pigment in the mixture is 5-95% by weight and the frit comprises at least 5% by weight of Al2O3, based on the weight of the frit, wherein the pearlescent pigment is based on a flake substrate and the ratio of the thickness of the flake substrate to the size of the frit particles is from 0.01 to 0.2.

US Pat. No. 10,214,649

HIGH CONTENT POLYAMIDE HOT-APPLIED THERMOPLASTIC COMPOSITION

1. A hot-applied thermoplastic pavement marking composition comprising:a modified polyamide resin from about 3 to about 10 weight percent;
a rosin-modified ester;
a copolymer;
a glass bead intermix of at least 30 weight percent;
a colored pigment from about 1 to about 15 weight percent; and
at least one of a plasticizer, an inorganic filler, a wax, an antioxidant or a light stabilizer;
wherein the glass bead intermix comprises AASHTO Type 1 glass beads and one of AASHTO Type 3 glass beads or AASHTO Type 4 glass beads, and the glass beads impart retro-reflectivity from about 200 to about 2000 mcd/m2/1x.

US Pat. No. 10,214,648

BISAZO DYES AND MIXTURES THEREOF

ARCHROMA IP GMBH, Reinac...

1. A compound of formula (I)
wherein K1 and K2 are independently unsubstituted or substituted aryl, and
wherein substituents of the substituted aryl are selected from the group consisting of H, —SO3H, unsubstituted or substituted, linear or branched C1-6 alkyl, unsubstituted or substituted, linear or branched C1-6 alkoxy or SO2Y, wherein Y is —OH, —CH?CH2 or —CH2CH2—Z, wherein Z is a leaving group which can be eliminated by OH? ions.

US Pat. No. 10,214,647

ELECTROPHORETIC PARTICLES AND PROCESSES FOR THE PRODUCTION THEREOF

E Ink Corporation, Bille...

1. A process for treatment of pigment particles bearing nucleophilic groups on their surfaces, the process comprising treating the pigment particles with a reagent having an electrophilic group but not bearing a polymerizable or polymerization-initiating group under conditions such that a residue of the reagent is chemically bonded to the pigment particle, the treatment of the pigment particle with the reagent changing the zeta potential of the pigment particle,wherein the reagent is an alkyl or aralkyl halide.

US Pat. No. 10,214,646

WARM MIX PAVING COMPOSITION W/LUBRICATING ANTISTRIP ADDITIVE

A.L.M. Holding Company, ...

1. An asphalt paving composition comprising functionally dry, essentially water-free, non-foamed asphalt binder containing lubricating antistrip additive mixed with uncompacted aggregate to provide a warm mix paving composition of the aggregate adequately coated with the functionally dry, essentially water-free, non-foamed asphalt binder and lubricating antistrip additive, wherein the lubricating antistrip additive reduces the mixing and compaction temperature of the warm mix paving composition such that the paving composition is produced at and is at a temperature of 280° F. or lower and can be compacted at a temperature of 260° F. or lower, and if the warm mix paving composition also comprises a lubricating wax, then the lubricating wax is 0.5 weight percent or less of the asphalt binder weight.

US Pat. No. 10,214,645

POLYMER BLEND FOR CABLE JACKETS

Nexans, Courbevoie (FR)

1. A cable, said cable comprising:one or more conductors; and
a jacket,
wherein said jacket is made from a composition including a polymer blend of thermoplastic polyurethane (TPU), and Polyvinylbutyral (PVB), with the ratio of PVB to TPU being up to 49% PVB by weight of the total weight of the polymer blend, the remainder of the polymer blend being TPU.

US Pat. No. 10,214,637

TIRE RUBBER COMPOSITION AND PNEUMATIC TIRE

SUMITOMO RUBBER INDUSTRIE...

1. A rubber composition for tires, comprising a diene rubber A modified with an acrylamide compound represented by Formula (I):wherein R1 represents hydrogen or a methyl group; R2 and R3 each represent a C1 to C4 alkyl group; and n represents an integer of 3 to 5, anda diene rubber B provided with a silicon compound as a coupling agent, which is tetrachlorosilicon, tetrabromosilicon, methyltrichlorosilicon, butyltrichlorosilicon, dichlorosilicon, or bistrichlorosilylsilicon, and a modifying compound represented by Formula (III) or with a modifying compound represented by Formula (III):
wherein R4 to R6 are the same as one another, each representing a methyl, ethyl, propyl, or butyl group; R7 to R12 are the same as one another, each representing a methoxy, ethoxy, propoxy or butoxy group; and p to r are the same as one another, each representing an integer of 3 to 5, wherein a polymer end of the diene rubber B is modified with the modifying compound represented by Formula (III), the combined modified diene rubbers A and B having a weight average molecular weight of 500,000 to 1,200,000,the blending ratio of the modified diene rubbers A and B (mass ratio of A/B) is 10/90 to 90/10,
the modified diene rubbers A and B each are a modified styrene butadiene rubber, and
the rubber composition further comprising silica having a CTAB specific surface area of 180 m2/g or more and a BET specific surface area of 185 m2/g or more.

US Pat. No. 10,214,634

ARTICLES FORMED WITH BIODEGRADABLE MATERIALS AND STRENGTH CHARACTERISTICS OF SAME

BIOLOGIQ, INC., Idaho Fa...

1. An article comprising:a starch-based polymeric material formed from a plasticizer and a mixture of starches including a first amount of a first starch and a second amount of a second starch; and
a polyolefin-based polymeric material;
wherein the article has a dart drop impact test value that is greater than: (i) a first dart drop impact test value of a first article including the polyolefin-based polymeric material and a first starch-based polymeric material formed from a single starch that is the first starch, and (ii) a second dart drop impact test value of a second article including the polyolefin-based polymeric material and a second starch-based polymeric material formed from a single starch that is the second starch.

US Pat. No. 10,214,633

TIRE WITH TREAD INTENDED FOR OFF-THE-ROAD SERVICE

1. A rubber composition comprised of, based on parts by weight per 100 parts by weight of elastomer (phr),(A) conjugated diene-based elastomers comprised of:
(1) about 80 to about 100 phr of natural cis 1,4-polyisoprene rubber, and
(2) up to about 20 phr of additional diene-based synthetic elastomer comprised of at least one of cis 1,4-polybutadiene rubber and styrene/butadiene rubber,
(B) about 20 to about 120 phr of rubber reinforcing filler comprised of a combination of pre-hydrophobated precipitated silica and rubber reinforcing carbon black, wherein said reinforcing filler is comprised of from about 5 to about 100 phr of rubber reinforcing carbon black, and wherein said pre-hydrophobated precipitated silica is comprised of a composite of precipitated silica pre-treated prior to addition to said rubber composition with bis(3-triethoxysillylpropyl) polysulfide having an average of from about 2 to about 4 connecting sulfur atoms in its polysulfidic bridge or with an alkoxyorganomercaptosilane, and
(C) from about 1 to about 50 phr of fatty acid amide, where said fatty acid amide is comprised of the general formula (I):

where R1 is comprised of an alkyl hydrocarbon radical containing from 12 to 36 carbon atoms, an alkenyl hydrocarbon radical containing from 12 to 36 carbon atoms or alkadiene hydrocarbon radical containing from 12 to 36 carbon atoms, and
wherein said styrene/butadiene rubber is at least one of:
(1) tin or silicon coupled styrene/butadiene/butadiene rubber and
(2) functionalized styrene/butadiene rubber containing functional groups reactive with hydroxyl groups contained on said pre-hydrophobated silica.

US Pat. No. 10,214,631

POLYMER COMPOSITION WITH IMPROVED LONG-TERM STABILITY, MOULDED PARTS PRODUCED HEREFROM AND ALSO PURPOSES OF USE

1. An ageing-resistant polymer composition with improved long-term stability, comprising, relative to the total composition,a) 82 to 99.7% by weight of at least one thermoplastic polymer or a blend of at least two thermoplastic polymers,
b) 0.2 to 11% by weight of carbon nanotubes,
c) 0.05 to 1.0% by weight of at least one antioxidant, selected from the group consisting of phenols, phosphites, phosphonites, amines, mixtures and combinations thereof,
d) 0.05 to 3% by weight of at least one mono- or polyfunctional epoxide compound and at least one metal deactivator,
wherein the mono- or polyfunctional epoxide compound comprises a group of the formula:

wherein R4 is the same or different at each occurrence and is selected from the group consisting of hydrogen and linear or branched alkyl radicals with 1 to 8 carbon atoms, and l is 0 or 1, and
e) 0 to 3% by weight of at least one additive.

US Pat. No. 10,214,629

CLASS OF ANTIOXIDANT AGENTS FOR POLYMER PRODUCTS

BRIDGESTONE CORPORATION, ...

1. A rubber mixture comprising:at least one polymer base having a cross-linkable unsaturated chain,
a vulcanization system, and
one or more antioxidant agents;
wherein said one or more antioxidant agents are compounds according to formula (I):

wherein, in formula (I), the substituents R1, R2, R3, R4 and R10, which are equal to or different from one another, are selected from the group consisting of —H, —OH, and —(CH2)nCHCH2 with n as an integer number ranging from 1 to 10; provided that, among the substituents R1, R2, R3, R4 and R10, at least one is —OH and at least one is —(CH2)nCHCH2; and
the substituents R5, R6, R7, R8 and R9, which are equal to or different from one another, are selected from the group consisting of —H, —OH, and —(CH2)nCHCH2 with n as an integer number ranging from 1 to 10; provided that, among the substituents R5, R6, R7, R8 and R9, at least one is —OH and at least one is —(CH2)nCHCH2.

US Pat. No. 10,214,626

RENEWABLE CROSS-LINKER FOR INCREASED BIO-CONTENT FROM FRUCTOSE

International Business Ma...

1. A composition comprising a compound having the general structure:wherein:each R1 includes a hetero-organic functional group selected from the group consisting of (CO)OR2, (CO)OH, (CH2)OH, NCO, (NH)(CO)OR2, (NH)(CO)NR2, NH2, (CH2)xOR3SH, (CH2)xO(CO)R3(SH), (CH2)xO(CO)R3(CH)?CH2, (CH2)xOR3(CH)?CH2, and (CH2)xO(CO)R2, or linked variations thereof,
when R1 includes R2, then R2 is a functional group that has a reactive end group,
when R1 includes R3, then R3 is an organic or hetero-organic group, and
x is 1 to 10.

US Pat. No. 10,214,624

APPARATUS AND METHOD FOR EXPANDING THERMALLY EXPANDABLE THERMOPLASTIC MICROSPHERES TO EXPANDED THERMOPLASTIC MICROSPHERES

AKZO NOBEL CHEMICALS INTE...

1. An apparatus for expanding thermally expandable thermoplastic microspheres, the apparatus comprising:a heating zone being capable of withstanding a pressure of at least 4 bars, the heating zone having an inlet pipe and an outlet pipe,
a pump for feeding a slurry of thermally expandable thermoplastic microspheres into the heating zone and capable of generating a pressure of at least 4 bars in the heating zone;
a means for heating the slurry of thermally expandable thermoplastic microspheres in the heating zone to a temperature of at least 60° C. without direct contact of the slurry to any fluid heat transfer medium; and
a distribution pipe having an inlet and an outlet, wherein the outlet pipe is attached to the distribution pipe between the inlet and the outlet of the distribution pipe.

US Pat. No. 10,214,623

SUBSTRATE-INDEPENDENTLY SURFACE-COATED POLYMER BY AROMATIC-AMINE COMPOUND AND COATING METHOD THEREOF

Core Biosystems Inc., Re...

1. A substrate-independently surface-coated polymer by an aromatic amine compound characterized in that the surface of a polymer substrate is modified in such a way to react, using a surface modifier, an aromatic amine compound of the following structural formula on at least one surface of the polymer substrate having a nucleophilic functional group or an electrophilic functional group,
wherein R1 is any of H, NH2 and NH-acyl.

US Pat. No. 10,214,622

CATALYST SYSTEMS FOR OLEFIN POLYMERIZATION

Dow Global Technologies L...

1. A procatalyst comprising a metal-ligand complex of formula (I):where:M is titanium, zirconium, or hafnium, each independently being in a formal oxidation state of +2, +3, or +4; and n is an integer from 0 to 3, and wherein when n is 0, X is absent;
each X independently is a monodentate ligand that is neutral, monoanionic, or dianionic; or two Xs are taken together to form a bidentate ligand that is neutral, monoanionic, or dianionic; and X and n are chosen in such a way that the metal-ligand complex of formula (I) is, overall, neutral;
each Z is O;
L is (C3-C40)hydrocarbylene or (C3-C40)heterohydrocarbylene, wherein the (C3-C40)hydrocarbylene has a portion that comprises a 3-carbon atom to 10-carbon atom linker backbone linking the Z atoms in formula (I) and the (C3-C40)heterohydrocarbylene has a portion that comprises a 3-atom to 10-atom linker backbone linking the Z atoms in formula (I), wherein each of the 3 to 10 atoms of the 3-atom to 10-atom linker backbone of the (C3-C40)heterohydrocarbylene independently is a carbon atom or heteroatom, wherein each heteroatom independently is O, S, S(O), S(O)2, Si(Rc)2, Ge(Rc)2, P(RP), —N?, or N(Rn), wherein independently each RC is (C1-C30)hydrocarbyl, each RP is (C1-C30)hydrocarbyl; and each RN is (C1-C30)hydrocarbyl;
R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R15 are independently selected from the group consisting of a (C1-C40)hydrocarbyl, (C1-C40)heterohydrocarbyl, Si(Rc)3, Ge(Rc)3, P(RP)2, N(RN)2, ORc, SRc, NO2, CN, CF3, RcS(O)—, RcS(O)2-, (Rc)2C=N—, RcC(O)O—, RcOC(O)—, RcC(O)N(R)—, (Rc)2NC(O)—, halogen atom, and hydrogen atom
when R8 is H, R9 is a (C1-C40)hydrocarbyl; (C1-C40)heterohydrocarbyl; Si(Rc)3, Ge(Rc)3, P(RP)2, N(RN)2, ORc, SRc, NO2, CN, CF3, RcS(O)—, RcS(O)2-, (Rc)2C?N—, RcC(O)O—, RcOC(O)—, RcC(O)N(R)—, (Rc)2NC(O)—or halogen atom; or
when R9 is H, R8 is a (C1-C40)hydrocarbyl; (C1-C40)heterohydrocarbyl; Si(Rc)3, Ge(Rc)3, P(RP)2, N(RN)2, ORc, SRc, NO2, CN, CF3, RcS(O)—, RcS(O)2-, (Rc)2C=N—, RcC(O)O—, RcOC(O)—, RcC(O)N(R)—, (Rc)2 NC(O)—or halogen atom; and
R1 and R16 are independently selected from radicals having formula (II)

 where each R22 and R19 is independently chosen from (C1-C20)alkyl, (C3-C40)cycloalkyl, (C6-C40)aryl, (C1-C40)heterohydrocarbyl, -Si(RC)3, -Ge(RC)3, -N(RN)2, -N?RC, -ORC;
optionally two or more of R2, R3, and R4, or two or more of R5, R6, R7, and R8, or two or more of R9, R10, R11, and R12, or two or more of R13, R14 and R15 can be covalently connect in ring structures, with such ring structures having from 3 to 50 atoms in the ring excluding any hydrogen atoms;
each of the aryl, heteroaryl, hydrocarbyl, heterohydrocarbyl, Si(RC)3, Ge(RC)3, P(RP)2, N(RN)2, ORC, SRC, RCS(O)—, RcS(O)2-, (RC)2C?N—, RCC(O)O—, RCOC(O)—, RCC(O)N(R)—, (RC)2NC(O)—, hydrocarbylene, and heterohydrocarbylene groups independently is unsubstituted or substituted with one or more Rs substituents; and
each Rs independently is a halogen atom, unsubstituted (C1-C18)alkyl, F3C—, FCH2O—, F2HCO—, F3CO—, R3Si—, R3Ge—, RO—, RS—, RS(O)—, RS(O)2—, R2P—, R2N—, R2C?N—, NC—, RC(O)O—, ROC(O)—, RC(O)N(R)—, or R2NC(O)—, or two of the Rs are taken together to form an unsubstituted (C1-C18)alkylene, wherein each R independently is an unsubstituted (C1-C18)alkyl.

US Pat. No. 10,214,619

PROCESS FOR PRODUCING FLUORINATED CROSSLINKED PRODUCT AND USE THEREOF

AGC Inc., Chiyoda-ku (JP...

1. A process for producing a fluorinated crosslinked product, the process comprising:irradiating a fluorinated polymer with active energy rays having a wavelength of from 150 to 300 nm,
wherein the fluorinated polymer is at least one member selected from the group consisting of:
a polymer consisting of a unit (1) and a unit (2),
wherein the unit (1) is represented by the following formula (1):

wherein X1 and X2 are each independently a hydrogen atom or a fluorine atom, Rf1 is a fluoroalkylene group or a fluoroalkylene group having at least two carbon atoms and an etheric oxygen atom between carbon-carbon atoms, Q1 is a single bond or an etheric oxygen atom, and Z1 is OH, OR1 or NR2R3, wherein R1 is an alkyl group, and R2 and R3 are each independently a hydrogen atom or an alkyl group,
wherein the unit (2) is at least one member selected from the group consisting of units represented by the following formulas (2-1) to (2-4):

wherein Q2 is a Cl-5 perfluoroalkylene group which optionally contains an etheric oxygen atom and in which some of fluorine atoms are optionally substituted by halogen atoms other than fluorine atoms;
a polymer consisting of the unit (1), the unit (2), and a unit (3), wherein the unit (3) is at least one unit derived from a fluoroethylene:
a polymer consisting of the unit (1), the unit (2), and a unit (4), wherein the unit (4) is at least one unit represented by the following formula (4):
—[CX3X4.CY1Y2]-  (4),
wherein X3 and X4 are each independently a hydrogen atom, a fluorine atom, or a chlorine atom, Y1 is a hydrogen atom, a fluorine atom, or a chlorine atom, Y2 is a hydrogen atom, a fluoroalkvl group which optionally contains an etheric oxygen atom between carbon-carbon atoms, a fluoroalkoxygroup which optionally contains an etheric oxygen atom between carbon-carbon atoms;
a polymer consisting of the unit (1), the unit (2), the unit (3), and the unit (4);
a polymer consisting of the unit (1), the unit (3), and the unit (4); and
a polymer consisting of the unit (1) and the unit (4),
wherein a proportion of the unit (1) is from 3 mol % to 50 mol % based on the total units in the fluorinated polymer.

US Pat. No. 10,214,617

DISSOLVING TIRE RUBBER

ASPHALT SCIENCES, LLC., ...

1. A method for generating a dissolved rubber compound comprising:receiving an asphalt compound;
heating the asphalt compound to a first temperature between 320° F. and 420° F.;
adding a tire rubber compound to the asphalt compound;
mixing the asphalt compound and the tire rubber compound for approximately 5 minutes to 240 minutes;
generating the dissolved rubber compound by heating a mixture of the asphalt compound and the tire rubber to a second temperature between 575° F. and 700° F., wherein there is little or no oxidation of the asphalt compound and the dissolved rubber compound; and
cooling the dissolved rubber compound.

US Pat. No. 10,214,614

COPOLYMERIZATION OF ETHYLENE OXIDE AND CARBON DIOXIDE

Cornell University, Itha...

1. A method of synthesizing a poly(ethylene carbonate) polymer,wherein the polymer is made up of Y, and optionally Z, the percentage of Y is greater than the percentage of Z, and the polymer has greater than 95% of Y,

the method comprising reacting ethylene oxide and carbon dioxide in the presence of a metal complex, wherein the metal complex is of the formula:

wherein:
M is a metal selected from zinc, cobalt, chromium, aluminum, titanium, ruthenium or manganese;
X is absent or is a nucleophilic ligand;
each instance of R3 is, independently, selected from hydrogen, halogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, and optionally substituted heteroaryl;
R7 and R9 are, independently, selected from hydrogen, halogen, —ORc, —OC(?O)Rc, —OC(?O)ORc, —OC(?O)N(Rd)2, —OSO2Rd, —C(?O)ORc, —C(?O)N(Rd)2, —CN, —CNO, —NCO, —N3, —NO2, —N(Rd)2, —N(Rd)C(?O)ORc, —N(Rd)C(?O)Rc, —N(Rd)SO2Rd, —SO2Rd, —SORd, —SO2N(Rd)2, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, wherein each instance of Rc is, independently, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, and each instance of Rd is, independently, hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl;
wherein the A value of at least one of R7 and R9 is greater than the A-value of tert-butyl; and
Ring A forms an optionally substituted 5- to 6-membered ring.

US Pat. No. 10,214,611

IMPACT MODIFIERS FOR EPOXY-BASED ADHESIVES

SIKA TECHNOLOGY AG, Baar...

1. Epoxy group-terminated impact modifier, comprising the reaction product ofa) two or more polyols of formula (I)

where
Y1 stands for an n-valent residue of a reactive polymer after the removal of terminal hydroxyl groups; and
n=2, 3 or 4;
b) one or more polyisocyanates of formula (II)

where
Y2 stands for a divalent residue of aliphatic, cycloaliphatic, aromatic or araliphatic diisocyanates after the removal of the isocyanate groups, or for a trivalent residue of trimers or biurets of aliphatic, cycloaliphatic, aromatic or araliphatic diisocyanates after the removal of the isocyanate groups; and
m=1 or 2; and
c) at least one epoxy resin comprising an epoxy compound of formula (III)

containing a primary or secondary hydroxy group,
where
Y3 stands for a residue of a primary or secondary hydroxyl group-containing aliphatic, cycloaliphatic, aromatic or araliphatic epoxy after the removal of the epoxy groups and of the primary or secondary hydroxyl group; and
q=1, 2 or 3,
wherein the polyols of formula (I) comprise
a1) at least one polyether polyol and
a2) an OH-terminated rubber having an OH functionality of less than or equal to 2, wherein the weight ratio of the polyether polyol to the OH-terminated rubber is in the range from 7:3 to 2:8; wherein when the epoxy group-terminated impact modifier is cured in a 2K adhesive with an epoxy resin the resin is cured at 0 to 80° C.

US Pat. No. 10,214,610

POLYMER AND COMPOSITION CONTAINING SAME

DNF CO., LTD., Daejeon (...

1. A polymer represented by Chemical Formula 1 or 2 below:
wherein
A and B are each independently selected from (C6-C20)arylene and (C3-C20)heteroarylene;
C is

wherein R11, R12, and R13 are independently selected from hydrogen, halogen, hydroxy and (C1-C20)alkyl;
A and B may be further be independently substituted with hydroxy, halogen, (C1-C20)alkyl, (C1-C20)alkoxy, (C3-C20)cycloalkyl, (C6-C20)aryl and (C3-C20)heteroaryl;
p and q are independently selected integers from 0 to 5, wherein p+q>0;
r is an integer from 1 to 5; and
m and n are each an independent integer from 1 to 1000.

US Pat. No. 10,214,607

CELL ADHESION INHIBITOR

JSR CORPORATION, Tokyo (...

1. A surface-modified tool having, on at least a portion of a surface thereof, a polymer comprising a repeating unit represented by the following formula (1):
wherein R3 represents a copolymer unit obtained by copolymerization of an acrylate monomer with a styrene monomer and R4 represents a monovalent group represented by the following formula (5) which includes one or more hydroxyl groups attached to a sulfinyl group,

wherein k1 is an integer of 1 to 4; k2 is an integer of 0 to 4; and *** denotes the position of bonding to a sulfur atom in formula (1).

US Pat. No. 10,214,606

RANDOM COPOLYMERS AS SOIL RELEASE AGENTS IN LAUNDRY PROCESSES

BASF SE, (DE)

1. A random copolymer obtained by polymerization of(i) at least one monomer according to formula (I):

in an amount of 38.5 to 70 mol %,
wherein n is 3 to 23, and
(ii) at least one monomer according to formula (II):

in an amount of 30 to 61.5 mol %.

US Pat. No. 10,214,602

POLYMERIZATION PROCESS FOR PRODUCING ETHYLENE BASED POLYMERS

Dow Global Technologies L...

1. A polymerization process for producing ethylene based polymers comprising:polymerizing ethylene and optionally one or more ?-olefins in the presence of one or more first catalyst systems and optionally one or more second catalyst systems in a single reactor, wherein first catalyst system comprises;
(a) one or more procatalysts comprising a metal-ligand complex of formula (I):

wherein:
M is titanium, zirconium, or hafnium, each independently being in a formal oxidation state of +2, +3, or +4; and n is an integer of from 0 to 3, and wherein when n is 0, X is absent; and each X independently is a monodentate ligand that is neutral, monoanionic, or dianionic; or two Xs are taken together to form a bidentate ligand that is neutral, monoanionic, or dianionic; and X and n are chosen in such a way that the metal-ligand complex of formula (I) is, overall, neutral; and L is (C3-C40)hydrocarbylene or (C3-C40)heterohydrocarbylene; and
each R1a and each R1b is independently (C1-C40)hydrocarbyl; (C1-C40)heterohydrocarbyl; Si(RC)3, Ge(RC)3, P(RP)2, N(RN)2, ORC, SRC, NO2, CN, CF3, RCS(O)—, RCS(O)2—, (RC)2C?N—, RCC(O)O—, RCOC(O)—, RCC(O)N(R)—, (RC)2NC(O)—, halogen atom,
R3, R6, R8, R9, R11, and R14 are independently selected from the group consisting of a (C1-C40)hydrocarbyl, (C1-C40)heterohydrocarbyl, Si(RC)3, Ge(RC)3, P(RP)2, N(RN)2, ORC, SRC, NO2, CN, CF3, RCS(O)—, RCS(O)2—, (RC)2C?N—, RCC(O)O—, RCOC(O)—, RCC(O)N(R)—, (RC)2NC(O)—, halogen atom, hydrogen atom, and combinations thereof;
when R8 is H, R9 is a (C1-C40)hydrocarbyl; (C1-C40)heterohydrocarbyl; Si(RC)3, Ge(RC)3, P(RP)2, N(RN)2, ORC, SRC, NO2, CN, CF3, RCS(O)—, RCS(O)2—, (RC)2C?N—, RCC(O)O—, RCOC(O)—, RCC(O)N(R)—, (RC)2NC(O)— or halogen atom; or
when R9 is H, R8 is a (C1-C40)hydrocarbyl; (C1-C40)heterohydrocarbyl; Si(RC)3, Ge(RC)3, P(RP)2, N(RN)2, ORC, SRC, NO2, CN, CF3, RCS(O)—, RCS(O)2—, (RC)2C?N—, RCC(O)O—, RCOC(O)—, RCC(O)N(R)—, (RC)2NC(O)— or halogen atom; wherein each RC, each RN, and each RP is independently (C1-C30)hydrocarbyl, and
optionally two or more the R3, R6, R8, R9, R11, and R14 groups can combine together into ring structures, with such ring structures having from 3 to 50 atoms in the ring excluding any hydrogen atoms;
each of the hydrocarbyl, heterohydrocarbyl, Si(RC)3, Ge(RC)3, P(RP)2, N(RN)2, ORC, SRC, RCS(O)—, RCS(O)2—, (RC)2C?N—, RCC(O)O—, RCOC(O)—, RCC(O)N(R)—, (RC)2NC(O)—, hydrocarbylene, and heterohydrocarbylene groups independently is unsubstituted or substituted with one or more RS substituents;
each RS independently is a halogen atom, polyfluoro substitution, perfluoro substitution, unsubstituted (C1-C18)alkyl, F3C—, FCH2O—, F2HCO—, F3CO—, R3Si—, R3Ge—, RO—, RS—, RS(O)—, RS(O)2—, R2P—, R2N—, R2C?N—, NC—, RC(O)O—, ROC(O)—, RC(O)N(R)—, or R2NC(O)—, or two of the RS are taken together to form an unsubstituted (C1-C18)alkylene, wherein each R independently is an unsubstituted (C1-C18)alkyl; and
(b) one or more cocatalysts; wherein the ratio of total number of moles of the one or more metal-ligand complexes of formula (I) to total number of moles of the one or more cocatalysts is from 1:10,000 to 100:1.

US Pat. No. 10,214,600

AMORPHPUS PROPYLENE-ETHYLENE COPOLYMERS

Eastman Chemical Company,...

1. An adhesive comprising 5 to 95 weight percent of a copolymer that comprises propylene and ethylene, said copolymer exhibiting at least one of the following sets of characteristics:(a) wherein said copolymer comprises:
at least 10 weight percent of ethylene,
a softening point in the range of 100 to 145° C.,
a needle penetration of less than 75 dmm,
a crystallinity of less than 20 percent as measured using DSC according to ASTM E 794-85, and
a Brookfield viscosity at 190° C. of less than 30,000 cps as measured according to ASTM D3236;
(b) wherein said copolymer comprises:
at least 10 weight percent of ethylene,
a softening point in the range of 85 to 145° C.,
a needle penetration of less than 75 dmm, and
a crystallinity of less than 10 percent as measured using DSC according to ASTM E 794-85; or
(c) wherein said copolymer comprises:
at least 10 weight percent of ethylene,
a softening point in the range of 119 to 145° C.,
a needle penetration of less than 75 dmm, and
a Brookfield viscosity at 190° C. of less than 30,000 cps as measured according to ASTM D3236.

US Pat. No. 10,214,599

METHOD FOR THE CONTINUOUS PRODUCTION OF ANIONIC POLYMERS USING RADICALS

COATEX, Genay (FR)

1. A method for continuously preparing an anionic polymer by radical polymerization, the method comprising:introducing at least one monomer selected from the group consisting of acrylic acid, methacrylic acid, and a mixture thereof; water; at least one initiator; and optionally at least one chain transfer agent into a tubular reactor, thus forming a fluid stream in the tubular reactor,
carrying out a polymerization reaction in the tubular reactor, optionally with a heating means to initiate the polymerization reaction and with a residence time in the reactor of greater than 1 min,
subjecting the fluid stream during the polymerization reaction to an oscillatory movement,
and
obtaining the anionic polymer in solution in water at an outlet of the tubular reactor,
wherein
the at least one monomer is optionally partially neutralized,
a temperature of the water is greater than 20° C.,
a solids content of the water solution of the anionic polymer is between 20% and 60% by weight, relative to a total weight of the anionic polymer, and a molecular weight Mw of less than 10 000 g/mol,
the tubular reactor has a length LR of at least 5 m and comprises at least one tubular section of length LS and internal diameter D such that LS is at least 20 times larger than D,
each tubular section comprises, over an entire length, a plurality of stationary baffles having holes, opposing the fluid stream, in a form of washers having a diameter identical to the internal diameter D of the tubular section,
each tubular section is connected to a device, which subjects the fluid stream to an oscillatory movement,
an amplitude of the oscillatory movement is from 0.3×d2 to 4×d2, wherein d2 is the external diameter of the stationary baffles,
a frequency of the oscillatory movement is from 0.1 to 100 Hz,
and
the residence time in the tubular reactor, size of the holes in the baffles, spacing of the baffles, and oscillatory movement of the device provides at any point in the tubular reactor, a homogeneous fluid stream.

US Pat. No. 10,214,598

(METH)ACRYLATE COMPOUND, AND COPOLYMER AND HOMOPOLYMER COMPRISING REPEATING UNIT DERIVED FROM SAME

LG CHEM, LTD., Seoul (KR...

1. A (meth)acrylate compound represented by the following Chemical Formula 1:
in Chemical Formula 1,
at least one of R1 and R2 is hydrogen and a remainder is an alkyl group having 1 to 10 carbon atoms,
L1 is —N(H)C(?O)N(H)—; or —N(H)C(?O)-L4-C(?O)N(H)—,
L2 to L4 are the same as or different from each other, and are each independently an alkylene group having 1 to 10 carbon atoms unsubstituted or substituted by an alkyl group,
in the case where L2 and L3 are the same as or different from each other and are each independently an unsubstituted alkylene group having 1 to 10 carbon atoms, one of R1 and R2 is an alkyl group having 1 to 10 carbon atoms,
m and n are each 1 or 2,
when m is 2, two L2s are the same as or different from each other, and
when n is 2, two L3s are the same as or different from each other.

US Pat. No. 10,214,597

DUAL-CURE CATIONICALLY POLYMERISABLE COMPOSITION AND METHOD FOR PRODUCING A COATING OR A COMPOSITE MATERIAL IMPLEMENTING SAID COMPOSITION

A ET A MADER, Lille (FR)...

1. A kit for a polymerisable composition, said kit comprising:I. a first portion A constituted by a composition comprising at least one monomer a1 that is reactive towards a cationic species or a Lewis or Brönsted acid species, and at least one co-initiator b;
II. a second portion B comprising at least one cationic salt e selected from the salts with formula S1, S3, and S4 below;
in which X represents a carbon atom or a sulfur atom; Y represents one or more stabilizing anionic species for the cationic species of the salt S1, or S3, or S4; R1 to R6, independently of one another, are selected from the following atom or atoms or group or groups, alone or in combination: a hydrogen atom; a nitro group —NO2; a cyano group —CN; a halogen atom; a C1-C20 alkyl group, a C1-C20 alkyl group substituted with one or more group(s) or one or more atom(s) selected independently from list I comprising the following groups or atoms: hydroxyl; carbonyl, alkenyl, aryl, heteroaryl, ether, ester, aldehyde, ketone, carboxylic acid, a halogen atom, primary amine, secondary amine, tertiary amine, primary amide, secondary amide, tertiary amide, urea, thioester, thiocarbonate, sulfoxide, sulfone, phosphine, phosphorane, phosphine oxide, cycloalkyl, heterocycloalkyl, or combinations thereof; a C1-C20 alkoxy group, a C1-C20 alkoxy group substituted with a C1-C20 alkyl group; a C1-C20 alkoxy group substituted with a C1-C20 alkyl group and one or more group(s) or one or more atom(s) selected equally well from list I; a C1-C20 alkoxy group substituted with one or more group(s) or one or more atom(s) selected equally well from list I, an aryl group; a heteroaryl group; a cycloalkyl group; a heterocycloalkyl group; an aryl group substituted with one or more group(s) independently selected from list I; an heteroaryl group substituted with one or more group(s) independently selected from list I; an heterocycloalkyl group substituted with one or more group(s) independently selected from list I; a cycloalkyl group substituted with one or more group(s) independently selected from list I; an acyl group; an aroyl group; an alkoxycarbonyl group; a carbamyl group.

US Pat. No. 10,214,594

WATER-SOLUBLE ESTERIFIED CELLULOSE ETHERS HAVING A LOW DEGREE OF NEUTRALIZATION

DOW GLOBAL TECHNOLOGIES L...

1. A hydroxypropyl methyl cellulose acetate succinate comprising acetyl groups and succinoyl groups, whereini) the degree of neutralization of the succinoyl groups is not more than 0.4,
ii) the total degree of ester substitution is from 0.10 to 0.70, and
iii) the hydroxypropyl methyl cellulose acetate succinate has a solubility in water of at least 2.0 weight percent at 2° C.

US Pat. No. 10,214,588

PROVIDING IMPROVED IMMUNOGLOBULIN SEQUENCES BY MUTATING CDR AND/OR FR POSITIONS

Ablynx N.V., Ghent-Zwijn...

1. Method for providing a library of nucleotide sequences that encode amino acid sequences that comprise or essentially consist of an immunoglobulin single variable domain that is a heavy chain variable domain and that forms a single functional antigen-binding unit, which method at least comprises the steps of:a) providing a pool of oligonucleotides that consists of (i) a series of at least two oligonucleotides that can be assembled, by means of PCR assembly, into a nucleotide sequence that encodes an amino acid sequence that comprises or essentially consists of an immunoglobulin single variable domain that is a heavy chain variable domain and that forms a single functional antigen-binding unit, and in addition (ii) at least one variant of at least one oligonucleotide of the at least two oligonucleotides that form part of the series, in which said at least one variant differs from said at least one oligonucleotide (and also from the other variants of said at least one oligonucleotide present in the pool, if any) in that it encodes an amino acid sequence that differs from the amino acid sequence encoded by said at least one oligonucleotide in the presence of one or more specific mutations;
b) subjecting the pool of oligonucleotides to PCR assembly; and
c) screening the library of nucleotide sequences obtained through steps a) and b) for nucleotide sequences that encode amino acid sequences that have one or more specific mutations,
or
testing one or more nucleotide sequences from the library of nucleotide sequences obtained through steps a) and b) as to whether they encode an amino acid sequence that has one or more specific mutations;wherein the oligonucleotides and the variants of said oligonucleotides used in step a) are such that each of the nucleotide sequences obtained as a result of the PCR assembly with a variant oligonucleotide in step b) encode an amino acid sequence that only contains one or more specific mutations in the amino acid residues at positions 27 to 35, 50 to 65 or 95 to 102 according to Kabat numbering that are generated following the rules described in i) or ii), wherein fori) the one or more specific mutations in the amino acid residues at positions 27 to 35, 50 to 65 or 95 to 102 according to Kabat numbering are generated by substituting the nucleotide sequences such that amino acid sequences with the following predetermined amino acid residue(s) are generated:
if the nucleotide sequence encodes K, substitute the nucleotide sequence such that an amino acid sequence with R is generated;
if the nucleotide sequence encodes R, substitute the nucleotide sequence such that an amino acid sequence with K is generated;
if the nucleotide sequence encodes A, substitute the nucleotide sequence such that an amino acid sequence with S or T or both is generated,
if the nucleotide sequence encodes S, substitute the nucleotide sequence such that an amino acid sequence with A or T or both is generated,
if the nucleotide sequence encodes T, substitute the nucleotide sequence such that an amino acid sequence with A or S or both is generated,
if the nucleotide sequence encodes I, substitute the nucleotide sequence such that an amino acid sequence with L or V or both is generated;
if the nucleotide sequence encodes L, substitute the nucleotide sequence such that an amino acid sequence with I or V or both is generated;
if the nucleotide sequence encodes V, substitute the nucleotide sequence such that an amino acid sequence with I or L or both is generated;
if the nucleotide sequence encodes F, substitute the nucleotide sequence such that an amino acid sequence with Y is generated;
if the nucleotide sequence encodes Y, substitute the nucleotide sequence such that an amino acid sequence with F is generated;
if the nucleotide sequence encodes N, substitute the nucleotide sequence such that an amino acid sequence with D is generated;
if the nucleotide sequence encodes D, substitute the nucleotide sequence such that an amino acid sequence with N is generated;
if the nucleotide sequence encodes Q, substitute the nucleotide sequence such that an amino acid sequence with E is generated;
if the nucleotide sequence encodes E, substitute the nucleotide sequence such that an amino acid sequence with Q is generated;
if the nucleotide sequence encodes G, substitute the nucleotide sequence such that an amino acid sequence with A is generated; or
if the nucleotide sequence encodes M, substitute the nucleotide sequence such that an amino acid sequence with L is generated; and wherein for
ii) the one or more specific mutations at positions 95 to 102 according to Kabat numbering are generated using the rules as above in i) and the one or more specific mutations at positions 27 to 35 or 50 to 65 according to Kabat numbering are generated by substituting the nucleotide sequences such that amino acid sequences with the following predetermined amino acid residue are generated:
any of F, G, R, and S in position 27;
any of A, I, S, and T in position 28;
any of F, G, L, and S in position 29;
any of D, G, S, and T in position 30;
any of D, I, N, S, and T in position 31;
any of D, N, and Y in position 32;
any of A, G, T, and V in position 33;
any of I, and M in position 34;
any of A, G, and S in position 35;
if amino acid sequence has an amino acid residue in position 52a in CDR2,
any of A, C, G, S, and T in position 50;
I in position 51;
any of N, R, S, and T in position 52;
any of R, S, T, and W in position 52a;
any of D, G, N, S, and T in position 53;
any of D, and G in position 54;
any of D, G, and S in position 55;
any of I, N, R, S, and T in position 56;
T in position 57;
any of D, H, N, S, and Y in position 58; or
if amino acid sequence has no amino acid residue in position 52a in CDR2,
any of A, G, R, S, and T in position 50;
I in position 51;
any of N, S, and T in position 52;
any of N, R, S, T, and Y in position 53;
any of D, G, R, and S in position 54;
any of G in position 55;
any of G, N, R, S, and T in position 56;
T in position 57;
any position of D, N, T, and Y in position 58.

US Pat. No. 10,214,571

PRODUCT MADE OF SILK

MorphoMed GmBH, Vienna (...

1. Method for the production of three-dimensional silk, wherein a three-dimensional silk product is treated with a silk solvent for a limited period of time so that a partial disintegration of the three-dimensional silk product is obtained whereafter the partially disintegrated silk product is re-stabilised with physical ?-sheet induction, by treatment with a re-stabilising solution, wherein the re-stabilising solution is formic acid and wherein the silk solvent comprises LiBr, LiSCN, 1-ethyl-3-methylimidazoliumacetate hexafluoro-2-propanol (HFIP), a mixture comprising ethanol and CaCl2, or a mixture comprising methanol and calcium nitrate; or mixtures thereof.

US Pat. No. 10,214,563

ANGIOTENSIN TYPE 2 (AT2) RECEPTOR AGONISTS AND USES THEREOF

LANTHIOPEP B.V., Groning...

1. A cyclic peptide compound consisting of the amino acid sequence Xaa1-Asp-Arg-Ile/Val-Xaa5-Ile/Val-His-Xaa8 comprising a thioether-bridge linkage between the side chains of Xaa5 and Xaa8 such that Xaa5 and Xaa8 together form a structure according to one of the general formula:
wherein R, R1, R2, R3, R4 and R5 are independently selected from the group consisting of —H and a C1-C10 alkyl or aralkyl group,
and wherein Xaa1 is selected from the group consisting of charged amino acids, aromatic amino acids and hydrophobic amino acids and protease-resistant variants thereof selected from D-stereoisomer or cyclized residue,
or a pharmaceutically acceptable salt thereof.

US Pat. No. 10,214,561

PEPTIDE HAVING ACTIVITY OF INHIBITING PRODUCTION OF TOXIN BY BACTERIUM BELONGING TO GENUS CLOSTRIDIUM

MIYARISAN PHARMACEUTICAL ...

1. A peptide represented by the following Formula (1):
in Formula (1), R1 is selected from the group consisting of an amino acid, ornithine, sarcosine, desmosine, isodesmosine, hydroxylysine, 3-hydroxyproline, 4-hydroxyproline, 2-aminoadipic acid, 3-aminoadipic acid, ?-alanine, ?-aminopropionic acid, 2-aminobutyric acid, 4-aminobutyric acid, 6-aminocapronic acid, 2-aminoheptanoic acid, 2-aminoisobutyric acid, and 3-aminoisobutyric acid, substituted or unsubstituted acyl group having 1 to 10 carbon atoms, substituted or unsubstituted benzyloxycarbonyl group, substituted or unsubstituted 9-fluorenylmethyloxycarbonyl group or substituted or unsubstituted phenylisothiocyanate group, and X1, X2, X3 and X4 are represented by any one of (1-1) to (1-4):
(1-1) X1 is Ala, Gly, Trp, Phe, Val, Leu, Ile, or Tyr; X2 is Phe, Trp or Tyr; X3 is Ala;
and X4 is His, Ala, Thr or Ser, with the proviso that, when X2 is Phe, X4 is Thr, and when X4 is Ala, X1 is Ala;
(1-2) X1 is Ala, X2 is Trp, X3 is Phe, and X4 is Ala;
(1-3) X1 is Leu, X2 is Trp, X3 is Phe, and X4 is Ser; and
(1-4) X1 is Leu, X2 is Phe, X3 is Trp, and X4 is Thr.

US Pat. No. 10,214,560

BRANCHED LINKER FOR PROTEIN DRUG CONJUGATES

LONZA LTD, Visp (CH) Lon...

1. A compound of formula (VI):
wherein
AA1 represents one alpha amino acid residue in which a carboxyl terminal thereof forms the shown amide bond to NH;

the alpha amino acid residue, AA1, having an alpha amino group denoted by structure (3);
R1 and R2 are identical or different and independently from each other selected from the group consisting of hydrogen and PGN;
PGN is a protecting group selected from the group consisting of Boc, Fmoc and benzyloxycarbonyl; and
AA1 is a residue of an amino aid selected from the group consisting of alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, lysine, lysine with side chain amino group protected with acetyl or formyl groups, arginine, histidine, ornithine, ornithine with side chain amino group protected with acetyl or formyl groups, and citrulline.

US Pat. No. 10,214,558

NATURAL AND SYNTHETIC COMPOUNDS FOR TREATING CANCER AND OTHER DISEASES

1. A compound having the structure:wherein R10 is selected from the group of CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-crotonoyl, CH2O-3,3-Dimethylacryloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, and CH2O-Ethylbutyryl; wherein R1, R2, R4, R5, and R8 are independently selected from the group of CH2OH , hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-Dimethylacryloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-Dimethylacryloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, and CH2O-ethylbutyryl; wherein R3 is OH or H; wherein R9, R11, R12, R13, R14, and R15 are CH3.

US Pat. No. 10,214,557

COMPOUNDS AND METHODS OF MAKING STEROLS USING DIOLS

Warsaw Orthopedic, Inc., ...

1. A method of making an oxysterol, the method comprising reacting a diol having the formula:
with a borane compound to form the oxysterol or a pharmaceutically acceptable salt or solvate thereof having the formula:

wherein R1 is a straight chain alkyl, and R2 is a straight chain alkyl, and the oxysterol is anhydrous.

US Pat. No. 10,214,555

METHOD FOR LIQUID-PHASE SYNTHESIS OF NUCLEIC ACID

TAKEDA PHARMACEUTICAL COM...

1. A compound represented by the following formula (I):
wherein
X represents a benzyl-type protective group,
R1 represents an aliphatic acyl-type protective group;
Y represents a hydroxyl protected group with a silyl-type protective group, a hydrogen atom, a halogen atom, cyano group, or a C1-6 alkoxy group;
Base represents

wherein each black circle denotes the site binding to the moiety of the following formula:

in the compound represented by the formula (I) above, and each asterisk denotes the site binding to another moiety of the compound represented by the formula (I) above to form said compound;
Z represents an oxygen atom;
ring Ar represents a benzene ring;
R2 represents an optionally substituted C10-30 alkoxy group;
R3 independently represents a halogen atom, cyano group, or optionally substituted C1-30 alkoxy group;
n represents an integer of 1 or 2;
with the proviso that no silyl or silyloxy substitutent moiety can include any Si—H moiety therein,
or a salt thereof.

US Pat. No. 10,214,554

PROCESS FOR MAKING CHLORO-SUBSTITUTED NUCLEOSIDE PHOSPHORAMIDATE COMPOUNDS

1. A process for making a compound of formula (i):wherein said process comprises the steps:(A) contacting a compound of Formula (B):
with pivaloyl chloride, in the presence of a base in an optional organic solvent A, for a time and at a temperature sufficient to provide a mixture of a compound of Formula (C) and a compound of formula (D):wherein P is pivaloyl and optional organic solvent A is selected from acetonitrile, toluene, dichloromethane, tetrahydrofuran, 2-methyltetrahydrofuran, ethyl acetate, isopropyl acetate, N,N-dimethylformamide, pyridine, N,N-dimethylacetamide and N-methylpyrrolidone, and mixtures thereof;(B) contacting the mixture of the compound of formula (C) and the compound of formula (D) with an oxidizing agent in an organic solvent B, in the presence of an optional pH modifier, for a time and at a temperature sufficient to provide a compound of Formula (E):
wherein P is pivaloyl and organic solvent B is selected from acetone, toluene, benzene, xylenes, cumene, cyclohexane, heptane, methylcyclohexane, dichloroethane, chlorobenzene, THF, anisole, ethyl acetate, isopropyl acetate, CPME, dichloromethane and mixtures thereof;(C) contacting the compound of Formula (E) with a compound of formula CH3MgX in the presence of a salt of formula R50Cl2 or (CH3)2AlX in an organic solvent C, for a time and at a temperature sufficient to provide a compound of Formula (F):
wherein P is pivaloyl; R50 is Mn or Zn; X is Br, Cl or I; and organic solvent C is selected from THF, 2-methyl THF, diethyl ether, dibutylether, cyclopentyl methyl ether, toluene, dimethoxyethane, anisole, xylenes and mixtures thereof;(D) contacting the compound of Formula (F) with a dehydrating agent, in the presence or absence of catalytic TMSCl or catalytic HCl or elemental sulfur, in an organic solvent D for a time and at a temperature sufficient to form a compound of formula (G):
wherein P is a pivaloyl group and organic solvent D is selected from toluene, benzene, xylenes, cumene, cyclohexane, heptane, methylcyclohexane, dichloroethane, chlorobenzene, THF, anisole, ethyl acetate, isopropyl acetate, CPME and mixtures thereof;(E) contacting the compound of formula (G) with a base in an organic solvent E for a time and at a temperature sufficient to provide a compound of Formula (A):
wherein organic solvent E is selected from organic alcohol solvents, toluene, benzene, xylenes, cumene, cyclohexane, heptane, methylcyclohexane, dichloroethane, chlorobenzene, DME, THF, anisole, ethyl acetate, isopropyl acetate, CPME, and mixtures thereof; and(F) contacting the compound of formula (A) with HCl or a compound of formula R(4-n)SiCln in an organic solvent E for a time and at a temperature sufficient to provide a compound of Formula (i), wherein R is C1-C6 alkyl or phenyl, and n is 1, 2 or 3.

US Pat. No. 10,214,551

ORGANIC ELECTROLUMINESCENT MATERIALS AND DEVICES

UNIVERSAL DISPLAY CORPORA...

1. A compound having the formula:
wherein G has the structure:

and wherein G is fused to any two adjacent carbon atoms on ring A;
wherein ring B, ring C, and ring D are 5- or 6-membered carbocyclic or heterocyclic aromatic rings;
wherein at least one of ring B and ring C is a 6-membered carbocyclic or heterocyclic aromatic ring;
wherein L1, L2, and L3 are independently selected from the group consisting of a single bond, BR, NR, PR, O, S, Se, C?O, S?O, SO2, CRR?, SiRR?, and GeRR?;
wherein at least one of L1, L2, and L3 is not a single bond;
wherein X is selected from the group consisting of BR, NR, PR, O, S, Se, C?O, S?O, SO2, CRR?, SiRR?, and GeRR?;
wherein Z1, Z2, Z3, and Z4 are nitrogen or carbon atoms;
wherein A1, A2, A3, A4, A5, A6, A7, and A8 comprise carbon or nitrogen;
wherein two adjacent atoms of A1, A2, A3, A4 are carbon atoms to which G is attached;
wherein R1, R2, R3, and R4 independently represent mono-, di-, tri-, or tetra-substitution;
wherein R1 is optionally fused, R2 is optionally fused to ring B, R3 is optionally fused to ring C, and R4 is optionally fused to ring D;
wherein R3 and R4 are optionally linked to form a ring;
wherein if L2 is not a single bond, R3 and L2 or R4 and L2 are optionally linked to form a ring;
wherein R, R?, R1, R2, R3, and R4 are independently selected from the group consisting of hydrogen, deuterium, halide, alkyl, cycloalkyl, heteroalkyl, arylalkyl, alkoxy, aryloxy, amino, silyl, alkenyl, cycloalkenyl, heteroalkenyl, alkynyl, aryl, heteroaryl, acyl, carbonyl, carboxylic acids, ester, nitrile, isonitrile, sulfanyl, sulfinyl, sulfonyl, phosphino, and combinations thereof; and
wherein at least one of the following is true:
(i) at least one of ring B and ring C comprises a carbene ligand coordinated to Pt;
(ii) Z2 and Z4 are nitrogen atoms; and
(iii) Z2 is a nitrogen atom and Z3 is a carbon atom.

US Pat. No. 10,214,550

BISPHOSPHITES HAVING AN UNSYMMETRIC OUTER BIPHENOL UNIT

Evonik Degussa GmbH, Ess...

1. A compound of formula (I):
wherein:
R1, R2, R3, R4, R5, R6, R7, R8 are each independently selected from the group consisting of —H, —(C1-C12)-alkyl, —O—(C1-C12)-alkyl, —O—(C6-C20)-aryl, —(C6-C20)-aryl, —S-alkyl, —S-aryl, halogen, COO—(C1-C12)-alkyl, CONH—(C1-C12)-alkyl, —CO—(C1-C12)-alkyl, —CO—(C6-C20)-aryl, —COOH, —OH, —SO3H, —CN, —NH2, and —N[(C1-C12)-alkyl]2;
R1?, R2?, R3?, R4?, R5?, R6?, R7?, R8?, R1?, R2?, R3?, R4?, R5?, R6?, R7?, R8? are each independently selected from the group consisting of —H, —(C1-C12)-alkyl, —O—(C1-C12)-alkyl, —O—(C6-C20)-aryl, —(C6-C20)-aryl, —S-alkyl, —S-aryl, halogen, COO—(C1-C12)-alkyl, CONH—(C1-C12)-alkyl, —CO—(C1-C12)-alkyl, —CO—(C6-C20)-aryl, —COOH, —OH, —SO3H, —NH2, and —N[(C1-C12)-alkyl]2; wherein
the alkyl and aryl groups may be substituted;
R1? and R8? are not the same radical; and
R1? and R8? are not the same radical.

US Pat. No. 10,214,549

FURAN-CONTAINING FLAME RETARDANT MOLECULES

International Business Ma...

1. A flame retardant molecule having the following chemical structure:
wherein X corresponds to a 2-methylfuran group, an alkyl group, or a phenyl group.

US Pat. No. 10,214,548

BORON CONTAINING SMALL MOLECULES AS ANTIPROTOZOAL AGENTS

Anacor Pharmaceuticals, I...

1. A compound having a structure according to the following formulae:whereinRa is substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkylor a salt thereof.

US Pat. No. 10,214,547

BETA-LACTAMASE INHIBITORS

VENATORX PHARMACEUTICALS,...

1. A compound represented by the following structures, or a stereoisomer thereof:

US Pat. No. 10,214,546

BTK INHIBITORS

1. A compound according to Formula I, or a pharmaceutically acceptable salt, thereof
wherein:
L is selected from the group consisting of:

R1 is H, cyano, halogen, (1-4C)alkyl, (3-6C)cycloalkyl, (1-3C)alkoxy, (3-6C)cycloalkoxy, morpholino, aryl or imidazolyl,
wherein (1-4C)alkyl or (1-3C)alkoxy may optionally be substituted with one, two or three halogens;
R2 is selected from H, (1-3C)alkyl, (1-3C)alkoxy, cyclopropyl, aminocarbonyl,
wherein the (1-3C)alkyl or (1-3C)alkoxy may optionally be substituted with hydroxyl or one, two or three halogen;
R2a is hydrogen or methyl;
R3a, R3b, R3c and R3d are each independently selected from H, halogen, (1-3C)alkyl, (1-6C)alkoxy, and (3-6C)cycloalkyl, wherein (1-3C)alkyl may be substituted with hydroxyl or one, two or three halogen;
R4 is independently selected from the group consisting of:
a) H,
b) halogen, and
c) haloalkyl;
wherein in ring system J-K:
Q is C?O or CH2;
T is C(Re)2, O, NRe, or a bond;
U is C(Rd)2, O, or NRd;
V is CH2 or O;
Rc is independently selected from H, fluoro, methyl or trifluoromethyl,
or two Rc groups can join to form a spirofused cyclopropyl group with the carbon atom to which they are attached;
Rd is independently selected from H, (1-3C)alkyl or trifluoromethyl;
Re is independently selected from H or (1-6C)alkyl,
or two Re groups can join to form a spirofused cyclopropyl group with the carbon atom to which they are attached;
when T is a bond, Q is C?O and U is C(Rd)2,
Rc and Rd can join to form a 3-6 membered ring with the carbons to which they are attached; and
with the proviso that:
when Q is CH2, then T is C(Re)2.

US Pat. No. 10,214,545

AMIDO-SUBSTITUTED IMIDAZOPYRIDAZINES USEFUL IN THE TREATMENT OF HYPER-PROLIFERATIVE AND/OR ANGIOGENESIS DISORDERS

BAYER PHARMA AKTIENGESELL...

1. A compound of formula (I):
in which:
represents a group selected from:group;wherein * indicates the point of attachment of said group with the rest of the molecule; and
represents a group selected from: R1-C?C—*, R1-CH?CH—*, R1-CH2—CH2—*, or
group;wherein * indicates the point of attachment of said group with the rest of the molecule; and
R1 represents a linear C1-C6-alkyl-, a branched C3-C6-alkyl-, or a C3-C6-cycloalkyl group which is optionally substituted, one or more times, independently from each other, with a substituent selected from:
a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C10-cycloalkyl-, aryl- optionally substituted one or more times, independently from each other, with an R substituent; —C(?O)NH2, —C(?O)N(H)R?, —C(?O)N(R?)R?, C(?O)OH, —C(?O)OR?, —NH2, —NHR?, —N(R?)R?, —N(H)C(?O)R?, —N(R?)C(?O)R?, —N(H)S(?O)R?, —N(R?)S(?O)R?, —N(H)S(?O)2R?, —N(R?)S(?O)2R?, —N?S(?O)(R?)R?, —OH, C1-C6-alkoxy-, C1-C6-haloalkoxy-, —OC(?O)R?, —OC(?O)NH2, —OC(?O)NHR?, —OC(?O)N(R?)R?, —SH, C1-C6-alkyl-S—, —S(?O)R?, —S(?O)2R?, —S(?O)2NH2, —S(?O)2NHR?, —S(?O)2N(R?)R? group;
R2 represents a hydrogen atom;
R3 represents a substituent selected from:
a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, —C(?O)R?, —C(?O)NH2, —C(?O)N(H)R?, —C(?O)N(R?)R?, —NH2, —NHR?, —N(R?)R?, —N(H)C(?O)R?, —N(R?)C(?O)R?, —N(H)C(?O)NH2, —N(H)C(?O)NHR?, —N(H)C(?O)N(R?)R?, —N(R?)C(?O)NH2, —N(R?)C(?O)NHR?, —N(R?)C(?O)N(R?)R?, —N(H)C(?O)OR?, —N(R?)C(?O)OR?, —NO2, —N(H)S(?O)R?, —N(R?)S(?O)R?, —N(H)S(?O)2R?, —N(R?)S(?O)2R?, —N?S(?O)(R?)R?, —OH, C1-C6-alkoxy-, C3-C6-cycloalkyl-C1-C6-alkoxy-, C1-C6-haloalkoxy-, —OC(?O)R?, —SH, C1-C6-alkyl-S—, —S(?O)R?, —S(?O)2R?, —S(?O)2NH2, —S(?O)2NHR?, —S(?O)2N(R?)R?, —S(?O)(?NR?)R? group; or a 4- to 7-membered nitrogen atom containing heterocycloalkyl group which is optionally substituted one or more times, independently from each other with a C1-C6-alkyl- group, said heterocycloalkyl group being attached to the rest of the molecule via a nitrogen ring atom of the heterocycloalkyl group; and said 6- to 10-membered cyclic amine group optionally containing one further heteroatom selected from the group consisting of O, N and S;
R4 represents a substituent selected from:
a hydrogen atom, a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C10-cycloalkyl-, 4- to 10-membered heterocycloalkyl-, aryl- optionally substituted one or more times, independently from each other, with an R substituent; heteroaryl- optionally substituted one or more times, independently from each other, with an R substituent; —C(?O)NH2, —C(?O)N(H)R?, —C(?O)N(R?)R?, —C(?O)OR?, —NH2, —NHR?, —N(R?)R?, —N(H)C(?O)R?, —N(R?)C(?O)R?, —N(H)C(?O)NH2, —N(H)C(?O)NHR?, —N(H)C(?O)N(R?)R?, —N(R?)C(?O)NH2, —N(R?)C(?O)NHR?, —N(R?)C(?O)N(R?)R?, —N(H)C(?O)OR?, —N(R?)C(?O)OR?, —NO2, —N(H)S(?O)R?, —N(R?)S(?O)R?, —N(H)S(?O)2R?, —N(R?)S(?O)2R?, —N?S(?O)(R?)R?, —OH, C1-C6-alkoxy-, C1-C6-haloalkoxy-, —OC(?O)R?, —OC(?O)NH2, —OC(?O)NHR?, —OC(?O)N(R?)R?, —SH, C1-C6-alkyl-S—, —S(?O)R?, —S(?O)2R?, —S(?O)2NH2, —S(?O)2NHR?, —S(?O)2N(R?)R?, —S(?O)(?NR?)R? group;
R5 represents a substituent selected from a hydrogen atom or C1-C6-alkyl-;
or:
R1 and R5 together with the nitrogen atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group, which is optionally substituted one or more times, independently from each other with a substituent selected from:
a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C10-cycloalkyl-, aryl- optionally substituted one or more times, independently from each other, with an R substituent; heteroaryl-optionally substituted one or more times, independently from each other, with an R substituent; —C(?O)NH2, —C(?O)N(H)R?, —C(?O)N(R?)R?, —C(?O)OH, —C(?O)OR?, —NH2, —NHR?, —N(R?)R?, —N(H)C(?O)R?, —N(R?)C(?O)R?, —N(H)S(?O)R?, —N(R?)S(?O)R?, —N(H)S(?O)2R?, —N(R?)S(?O)2R?, —N?S(?O)(R?)R?, —OH, C1-C6-alkoxy-, C1-C6-haloalkoxy-, —OC(?O)R?, —OC(?O)NH2, —OC(?O)NHR?, —OC(?O)N(R?)R?, —SH, C1-C6-alkyl-S—, —S(?O)R?, —S(?O)2R?, —S(?O)2NH2, —S(?O)2NHR?, —S(?O)2N(R?)R? group;
said 6- or 7-membered heterocycloalkyl group optionally containing one further heteroatom selected from the group consisting of O, N and S;
R represents a substituent selected from:
a halogen atom, a —CN, C1-C6-alkyl-, C1-C6-haloalkyl-, C2-C6-alkenyl-, C2-C6-alkynyl-, C3-C10-cycloalkyl-, 4- to 10-membered heterocycloalkyl-, aryl-, heteroaryl-, —C(?O)R?, —C(?O)NH2, —C(?O)N(H)R?, —C(?O)N(R?)R?, —C(?O)OR?, —NH2, —NHR?, —N(R?)R?, —N(H)C(?O)R?, —N(R?)C(?O)R?, —N(H)C(?O)NH2, —N(H)C(?O)NHR?, —N(H)C(?O)N(R?)R?, —N(R?)C(?O)NH2, —N(R?)C(?O)NHR?, —N(R?)C(?O)N(R?)R?, —N(H)C(?O)OR?, —N(R?)C(?O)OR?, —NO2, —N(H)S(?O)R?, —N(R?)S(?O)R?, —N(H)S(?O)2R?, —N(R?)S(?O)2R?, —N?S(?O)(R?)R?, —OH, C1-C6-alkoxy-, C1-C6-haloalkoxy-, —OC(?O)R?, —OC(?O)NH2, —OC(?O)NHR?, —OC(?O)N(R?)R?, —SH, C1-C6-alkyl-S—, —S(?O)R?, —S(?O)2R?, —S(?O)2NH2, —S(?O)2NHR?, —S(?O)2N(R?)R?, —S(?O)(?NR?)R? group;
R? and R? represent, independently from each other, a substituent selected from:
a C1-C6-alkyl-, C3-C10-cycloalkyl-, C1-C6-haloalkyl-, C1-C3-alkoxy-C2-C6-alkyl- group;
n represents an integer of 0, 1, 2, 3, 4 or 5 when
represents a:group;or
n represents an integer of 0, 1, 2, 3 or 4 when
represents a group selected from:group;or a stereoisomer, a tautomer, an N-oxide, or a salt thereof, or a mixture of same.

US Pat. No. 10,214,544

IMIDAZOPYRIDAZINE AND IMIDAZOTHIADIAZOLE COMPOUNDS

Universite De Montreal, ...

1. A compound of Formula I:or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein:the dashed line represents an optional double-bond with the proviso that only one of the two dashed line double bonds exists at the same time;
X1 is O and X2 is CR1a or N; or
X1 is N and X2 is O; or
X1 is N or CR1a, and X2 is S; or
X1 is N and X2 is NR8; or
X1 is NR8 and X2 is N; or
X1 is NR8 and X2 is CR1a; or
X1 is CR1a and X2 is NR8;
Y is S or —CR2a?CR2a—;
X3, X4 and X5 are independently selected from C(R9) or N;
W is O or S;
R1 is —N(R6)—C(O)—R7or —N(R6)—S(O)2—R7;

 is selected from the group consisting of a phenyl ring, or a 6-membered heteroaryl ring containing at least one nitrogen atom,or alternately the moietyis selected from
R1a is selected from the group consisting of H, halo, cyano, C1-C4 alkyl, C3-C5 cycloalkyl and C1-C4 alkoxy;
R2 is H, halo, C1-C6 alkyl, C1-C3 alkoxy, CN or C3-C7 cycloalkyl;
R2a is independently at each occurrence selected from the group consisting of H, halo, CN, C1-C3 alkyl, C1-3 haloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy;
R3 is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, C1-C2 haloalkyl, C1-C2 haloalkoxy, C3-C6 cycloalkyl, C2-C3 alkenyl, C2-C3 alkynyl and halo;
R4 and R5 are independently selected from H, C1-C6 alkyl, C1-C4 fluoroalkyl, and C1-C4 hydroxyalkyl, or R4 and R5 can be taken together with the carbon to which they are attached to form a C3-C7 cycloalkyl ring;
R6 is selected from H, C1-C6 alkyl, C1-C3haloalkyl, or C1-C3hydroxyalkyl; and
R7 is selected from the group consisting of hydrogen, C2-C6 alkyl, C6-C10 aryl, C1-C7 alkoxy, 5-7 membered heterocyclic ring containing 1-3 hetero atoms independently selected from N, O or S, C3-7 cycloalkyl, and 6-10 membered heteroaryl, wherein each of said alkyl, cycloalkyl, aryl, heterocylic and heteroaryl group is independently unsubstituted or substituted with 1-3 moieties which can be the same or different and being independently selected from the group consisting of halo, alkyl, haloalkyl, aryl, heteroaryl, alkoxy, haloalkoxy, aryloxy, arylalkyloxy, alkyloxycarbonyl, alkylcarboxy, aryloxycarbonyl, arylcarboxy, nitro, cyano, OH, NH2, NH(alkyl), N(alkyl)2, CONR10R11, SONR10R11, NR10SO2R11, NR10COR11, NR10CONR10R11COOH, COOR10, oxo and methylenedioxy, wherein R10 and R11 are the same or different and are H or C1-4 alkyl or R10 and R11 can be taken together with the N to which they are attached to form a 4-7 membered heterocycle ring;
or R6 and R7 may be taken together to form a monocyclic or bicyclic heterocyclic ring with 0-2 additional heteroatoms selected independently from N, O, or S, wherein each of said monocyclic or bicyclic heterocylic ring can be independently unsubstituted or substituted with 1-3 moieties which can be the same or different and being independently selected from the group consisting of halo, alkyl, aryl, heteroaryl, alkoxy, aryloxy, arylalkyoxy, alkyloxycarbonyl, alkylcarboxy, aryloxycarbonyl, arylcarboxy, nitro, cyano, OH, NH2, NH(alkyl), N(alkyl)2, CONR12R13, SONR12R13, NR12SO2R13, NR12COR13, NR12CONR12R13, COOH, COOR12, oxo and methylenedioxy, wherein R12 and R13 are the same or different and are H or C1-4 alkyl, or R12 and R13 can be taken together with the N to which they are attached to form a 4-7 membered heterocycle ring,
R8 is H or C1-C4 alkyl; and
R9 is selected from the group consisting of H, halo, C1-C6 alkyl, C1-6 haloalkyl, - C1-C6 alkoxy and C1C3 haloalkoxy;
with the proviso that when Y is S and A is

 then R7 is not pyridizin-4-yl.

US Pat. No. 10,214,543

SYNTHESIS OF CEPHALOSPORIN COMPOUNDS

1. A process of making a compound of formula (V?):
comprising admixing a compound of formula (III?):

and a compound of formula (IV?):

in a solvent to provide the compound of formula (V?),
wherein:
P1 and P2 are each independently an acid-labile nitrogen protecting group,
P3 and P4 are each independently an acid-labile oxygen protecting group,
X? is a pharmaceutically acceptable salt,
Y is Cl or Br;
the molar ratio of the compound of formula (IV?) to the compound of formula (III?) is from 1.0:1 to 1.3:1; and
the solvent is purged with nitrogen at from 0.2 m3/h to 1.2 m3/h per kilogram of the compound of formula (III?).

US Pat. No. 10,214,542

MODIFIED MACROCYCLIC COMPOUNDS

BAYER PHARMA AKTIENGESELL...

1. A compound of formula (I)
wherein:
A is a bivalent moiety selected from the group consisting of —S—, —S(?O)—, —S(?O)2—, and —S(?O)(?NR5)—;
G and E are independently a bivalent moiety selected from the group consisting of —O—, —N(RA)—, —CH2—, —CH(C1-C6-alkyl)-, —C(C1-C6-alkyl)2-, —S—, —S(?O)—, and —S(?O)2—,
with the proviso that at least one of said bivalent moieties G and E is different from —O—;
L is a C2-C8-alkylene moiety,
wherein said moiety is optionally substituted with
(i) one substituent selected from the group consisting of hydroxy, —NR6R7, C2-C3-alkenyl-, C2-C3-alkynyl-, C3-C4-cycloalkyl-, hydroxy-C1-C3-alkyl, and —(CH2)NR6R7, and/or
(ii) one or two or three or four substituents independently selected from the group consisting of halogen and C1-C3-alkyl-,
or wherein
one carbon atom of said C2-C8-alkylene moiety forms a three- or four-membered ring together with a bivalent moiety to which it is attached, wherein said bivalent moiety is selected from the group consisting of —CH2CH2—, —CH2CH2CH2—, and —CH2OCH2—;
X and Y are CH or N, with the proviso that one of X and Y is CH and one of X and Y is N;
R1 is a group selected from the group consisting of C1-C6-alkyl-, C3-C6-alkenyl-, C3-C6-alkynyl-, C3-C7-cycloalkyl-, heterocyclyl-, phenyl-, heteroaryl-, phenyl-C1-C3-alkyl- and heteroaryl-C1-C3-alkyl-,
wherein said group is optionally substituted with one or two or three substituents independently selected from the group consisting of hydroxy, cyano, halogen, C1-C6-alkyl-, halo-C1-C3-alkyl-, C1-C6-alkoxy-, C1-C3-fluoroalkoxy-, —NH2, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, —OP(?O)(OH)2, —C(?O)OH, and —C(?O)NH2;
R2 is a group selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, cyano, C1-C3-alkyl-, C1-C3-alkoxy-, halo-C1-C3-alkyl-, and C1-C3-fluoroalkoxy-;
R3 and R4 are independently a group selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, cyano, C1-C3-alkyl-, C1-C3-alkoxy-, halo-C1-C3-alkyl-, and C1-C3-fluoroalkoxy-;
R5 is a group selected from the group consisting of a hydrogen atom, cyano, —C(?O)R8, —C(?O)OR8, —S(?O)2R8, —C(?O)NR6R7, C1-C6-alkyl-, C3-C7-cycloalkyl-, heterocyclyl-, phenyl-, and heteroaryl-,
wherein said C1-C6-alkyl-, C3-C7-cycloalkyl-, heterocyclyl-, phenyl- or heteroaryl-group is optionally substituted with one, two or three substituents independently selected from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl-, C1-C3-alkoxy-, —NH2, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C1-C3-alkyl-, and C1-C3-fluoroalkoxy-;
R6 and R7 are independently a group selected from the group consisting of a hydrogen atom, C1-C6-alkyl-, C3-C7-cycloalkyl-, heterocyclyl-, phenyl-, benzyl- and heteroaryl-,
wherein said C1-C6-alkyl-, C3-C7-cycloalkyl-, heterocyclyl-, phenyl-, benzyl- or heteroaryl-group is optionally substituted with one, two or three substituents independently selected from the group consisting of halogen, hydroxy, C1-C3-alkyl-, C1-C3-alkoxy-, —NH2, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C1-C3-alkyl-, and C1-C3-fluoroalkoxy-,
or
R6 and R7 are taken together with the nitrogen atom to which they are attached to form a cyclic amine;
R8 is a group selected from the group consisting of C1-C6-alkyl-, halo-C1-C3-alkyl-, C3-C7-cycloalkyl-, heterocyclyl-, phenyl-, benzyl- and heteroaryl-,
wherein said group is optionally substituted with one, two or three substituents independently selected from the group consisting of halogen, hydroxy, C1-C3-alkyl-, C1-C3-alkoxy-, —NH2, alkylamino-, dialkylamino-, acetylamino-, N-methyl-N-acetylamino-, cyclic amines, halo-C1-C3-alkyl-, and C1-C3-fluoroalkoxy-; and
RA is a hydrogen atom or a C1-C6-alkyl-group,
or an enantiomer, a diastereomer, a salt, or a solvate thereof, or a salt of said solvate.

US Pat. No. 10,214,541

DIARYL MACROCYCLES AS MODULATORS OF PROTEIN KINASES

TP Therapeutics, Inc., S...

1. A compound of the formulawhereineach L1 and L2 is independently —C(R1?)(R2?)—, —O—, —N(Rk?)—, —S—, —S(O)— or —S(O)2—;
each R1? and R2? is independently H, deuterium, halogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-10 aryl, mono- or bicyclic heteroaryl, —ORa?, —OC(O)Ra?, —OC(O)NRa?Rb?, —OS(O)Ra?, —OS(O)2Ra?, —SRa?, —S(O)Ra?, —S(O)2Ra?, —S(O)NRa?Rb?, —S(O)2NRa?Rb?, —OS(O)NRa?Rb?, —OS(O)2NRa?Rb?, —NRa?Rb?, —NRa?C(O)Rb?, —NRa?C(O)ORb?, —NRa?C(O)NRa?Rb?, —NRa?S(O)Rb?, —NRa?S(O)2Rb?, —NRa?S(O)NRa?Rb?, —NRa?S(O)2NRa?Rb?, —C(O)Ra?, —C(O)ORa?, —C(O)NRa?Rb?, —PRa?Rb?—P(O)Ra?Rb?, —P(O)2Ra?Rb?, —P(O)NRa?Rb?, —P(O)2NRa?Rb?, —P(O)ORa?, —P(O)2ORa?, —CN, or —NO2; or R1? and R2? taken together with the carbon or carbons to which they are attached form a C3-6cycloalkyl or a 4- to 6-membered heterocycloalkyl, wherein each hydrogen atom in C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-10 aryl, mono- or bicyclic heteroaryl, 4- to 6-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-6alkyl, C1-6haloalkyl, —ORe?, —OC(O)Re?, —OC(O)NRe?Rf?, —OS(O)Re?, —OS(O)2Re?, —OS(O)NRe?Rf?, —OS(O)2NRe?Rf?, —SRe?, —S(O)Re?, —S(O)2Re?, —S(O)NRe?Rf?, —S(O)2NRe?Rf?, —NRe?Rf?, —NRe?C(O)Re?, —NRe?C(O)ORf?, —NRe?C(O)NRe?Rf?, —NRe?S(O)Rf?, —NRe?S(O)2Rf?, —NRe?S(O)NRe?Rf?, —NRe?S(O)2NRe?Rf?, —C(O)Re?, —C(O)ORe?, —C(O)NRe?Rf?, —PRe?Rf?, —P(O)Re?Rf?, —P(O)2Re?Rf?, —P(O)NRe?Rf?, —P(O)2NRe?Rf?, —P(O)ORe?, —P(O)2ORe?, —CN, or —NO2;
each Rk? is independently H, deuterium, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-10 aryl, or mono- or bicyclic heteroaryl, wherein each hydrogen atom in C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-10 aryl, or mono- or bicyclic heteroaryl is independently optionally substituted by deuterium, halogen, C1-6alkyl, C1-6haloalkyl, —ORe?, —OC(O)Re?, —OC(O)NRe?Rf?, —OS(O)Re?, —OS(O)2Re?, —OS(O)NRe?Rf?, —OS(O)2NRe?Rf?, —SRe?, —S(O)Re?, —S(O)2Re?, —S(O)NRe?Rf?, —S(O)2NRe?Rf?, —NRe?Rf?, —NRe?C(O)Rf?, —NRe?C(O)ORf?, —NRe?C(O)NRe?Rf?, —NRe?S(O)Rf?, —NRe?S(O)2Rf?, —NRe?S(O)NRe?Rf?, —NRe?S(O)2NRe?Rf?, —C(O)Re?, —C(O)ORe?, —C(O)NRe?Rf?, —PRe?Rf?, —P(O)Re?Rf?, —P(O)2Re?Rf?, —P(O)NRe?Rf?, —P(O)2NRe?Rf?, —P(O)ORe?, —P(O)2ORe?, —CN, or —NO2;
each R3? and R4? is independently deuterium, halogen, —ORc?, —OC(O)Rc?, —OC(O)NRc?Rd?, —OC(?N)NRc?Rd?, —OS(O)Rc?, —OS(O)2Rc?, —OS(O)NRc?Rd?, —OS(O)2NRc?Rd?, —SRc?, —S(O)Rc?, —S(O)2Rc?, —S(O)NRc?Rd?, —S(O)2NRc?Rd?, —NRc?Rd?, —NRc?C(O)Rd?,—NRc?C(O)ORd?, —NRc?C(O)NRc?Rd?, —NRc?C(?N)NRc?Rd?, —NRc?S(O)Rd?, —NRc?S(O)2Rd?, —NRc?S(O)NRc?Rd?, —NRc?S(O)2NRc?Rd?, —C(O)Rc?, —C(O)ORc?, —C(O)NRc?Rd?, —C(?N)NRc?Rd?, —PRc?Rd?, —P(O)Rc?Rd?, —P(O)2Rc?Rd?, —P(O)NRc?Rd?, —P(O)2NRc?Rd?, —P(O)ORc?, —P(O)2ORc?, —CN, —NO2, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-10 aryl, or mono- or bicyclic heteroaryl, or any two R3? groups or any two R4? groups taken together with the ring to which they are attached form a C5-8cycloalkyl or a 5- to 8-membered heterocycloalkyl, wherein each hydrogen atom in C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-10 aryl, mono- or bicyclic heteroaryl C5-8cycloalkyl or a 5- to 8-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-6alkyl, C1-6haloalkyl, —ORe?, —OC(O)Re?, —OC(O)NRe?Rf?, —OS(O)Re?, —OS(O)2Re?, —OS(O)NRe?Rf?, —OS(O)2NRe?Rf?, —SRe?, —S(O)Re?, —S(O)2Re?, —S(O)NRe?Rf?, —S(O)2NRe?Rf?, —NRe?Rf?, —NRe?C(O)Rf?, —NRe?C(O)ORf?, —NRe?C(O)NRe?Rf?, —NRe?S(O)Rf?, —NRe?S(O)2Rf?, —NRe?S(O)NRe?Rf?, —NRe?S(O)2NRe?Rf?, —C(O)Re?, —C(O)ORe?, —C(O)NRe?Rf?, —PRe?Rf?, —P(O)Re?Rf?, —P(O)2Re?Rf?, —P(O)NRe?Rf?, —P(O)2NRe?Rf?, —P(O)ORe?, —P(O)2ORe?, —CN, or —NO2;
R7? is H, deuterium, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-10 aryl, or mono- or bicyclic heteroaryl, wherein each hydrogen atom in C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-10 aryl, or mono- or bicyclic heteroaryl is independently optionally substituted by deuterium, halogen, —ORi?, —OC(O)Ri?, —OC(O)NRi?Rj?, —OS(O)Ri?, —OS(O)2Ri?, —OS(O)NRi?Rj?, —OS(O)2NRi?Rj?, —SRi?, —S(O)Ri?, —S(O)2Ri?, —S(O)NRi?Rj?, —S(O)2NRi?Rj?, —NRi?Rj?, —NRi?C(O)Rj?, —NRi?C(O)ORj?, —NRi?C(O)NRi?Rj?, —NRi?S(O)Rj?, —NRi?S(O)2Rj?, —NRi?S(O)NRi?Rj?, —NRi?S(O)2NRi?Rj?, —C(O)Ri?, —C(O)ORi?, —C(O)NRi?Rj?, —PRi?Rj?, —P(O)Ri?Rj?, —P(O)2Ri?Rj?, —P(O)NRi?Rj?, —P(O)2NRi?Rj?, —P(O)ORi?, —P(O)2ORi?, —CN, or —NO2;
each Ra?, Rb?, Rc?, Rd?, Re?, Rf?, Ri? and Rj? is independently selected from the group consisting of H, deuterium, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-10 aryl, and heteroaryl;
m? is 2, 3, 4, or 5;
n? is 2, 3, or 4;
p? is 0, 1, 2, 3, or 4; and
q? is 0, 1, 2, 3, or 4;or a pharmaceutically acceptable salt thereof.

US Pat. No. 10,214,540

COMPOUND HAVING AGONISTIC ACTIVITY ON SOMATOSTATIN RECEPTOR, AND USE THEREOF FOR MEDICAL PURPOSES

ONO PHARMACEUTICAL CO., L...

1. A compound of the following formula (I):
wherein
R1 is (1) halogen, (2) hydroxyl, (3) C1-4 alkyl which may be substituted with substituents selected from the group consisting of (a) —OR7 and (b) halogen, (4) C1-4 alkoxy, or (5) C3-8 cycloalkyl;
p is an integer of 0 to 3;
when p is 2 or more, each R1 may be same or different;
R2 is (1) halogen, (2) oxo, (3) —OR3, (4) —COR4, (5) —COOR5, (6) —SO2R6, (7) C1-4 alkyl which may be substituted with substituents selected from the group consisting of (a) —OR7, (b) —COR8, (c) —COOR9, (d) —SO2R10, (e) halogen, and (f) cyano, (8) C3-6 monocyclic carbon ring which may be substituted with substituents selected from the group consisting of (a) C1-4 alkyl, (b) phenyl, and (c) hydroxymethyl, (9) 5 to 6 membered monocyclic hetero ring which may be substituted with substituents selected from the group consisting of (a) C1-4 alkyl, (b) phenyl, and (c) hydroxymethyl, (10) —NR76R77, (11) —CONR78R79, (12) —NR80COR81 or (13) cyano;
R3 and R7 are independently (1) hydrogen, (2) C1-4 alkyl, (3) C1-4 haloalkyl, or (4) —COR4;
R4 and R8 are independently C1-4 alkyl or amino;
R5, R6, R9 and R10 are independently hydrogen or C1-4 alkyl;
R76 to R81 are independently hydrogen or C1-4 alkyl;
q is an integer of 0 to 3;
when q is 2 or more, more than one R2 may be same or different;
Ring A is benzene, benzimidazole, indazole, indole, imidazole, triazole, pyrazole, pyridine, pyrimidine, thiophene, oxazole, thiazole, or oxadiazole;
Ring G is benzene;
Y in Ring B is N or CH;
L is (1) bond, (2) —CR21?CR22?, (3) —X?, (4) —X—CR23R24?, (5) —CR25R26—X?, (6) —X—CR27R28—O?, (7) —X—O—CR29R30?, (8) —O—CR31R32—X?, or (9) —CR33R34—O—X?, wherein the arrow is a binding position in each group;
R21 to R34 is independently hydrogen or C1-4 alkyl;
X is (1) —O—, (2) —C(?O)—, (3) —NR41—, (4) —C(?O)—NR42—, or (5) —NR43—C(?O)—;
R41 to R43 are independently hydrogen or C1-4 alkyl;
M is (1) bond, (2) —O—(C1-3 alkylene)-, or (3) —(C1-3 alkylene)-O—;
Z is pyrrolidine, piperidine, or octahydropyridooxazine, which each may be substituted with the substituents selected from the group consisting of (a) halogen, (b) —NR53R54, (c) —OR55, (d) C1-4 alkyl which may be substituted with —NR56R57 and/or —OR58, and (e) oxo, with the proviso that Z is not piperidine, when M is bond and Y in Ring B is N;
R53 to R58 are independently hydrogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 acyl, —C(?O)—O—(C1-4 alkyl), —C(?O)—OCH2R68, oxetanyl, or oxolanyl; and
R68 is (1) C5-6 monocyclic carbon ring which may be substituted with the substituents selected from the group consisting of (a) C1-4 alkyl and (b) oxo, or (2) 5 to 6 membered monocyclic hetero ring which may be substituted with the substituents selected from the group consisting of (a) C1-4 alkyl and (b) oxo,
a salt thereof, an N-oxide thereof, or a solvate thereof,
with the proviso that the following compounds are excluded:
1,3-diphenyl-2-(1-pyrrolidinyl)benzene, 1,3-diphenyl-2-(1-piperidinyl)benzene, N-[2-(2,6-diphenylphenoxy)ethyl]piperidine, N-[2-(2,6-diphenylphenoxy)ethyl]-N-methylpiperidinium tetrafluoroborate, and N-[3-(2,6-diphenylphenoxy)propyl]-N-methylpiperidinium tetrafluoroborate.

US Pat. No. 10,214,539

INTERMEDIATES AND METHODS FOR THE SYNTHESIS OF HALICHONDRIN B ANALOGS

1. A compound of formula (I):
wherein:
z is a single or double bond, provided that when z is a double bond, X2 is C and Y1 is hydrogen; and
provided that when z is a single bond, X2 is CH or O;
X1 is O, S, or CN, provided that when X1 is CN or S, X2 is O;
Y1 is a halide, hydrogen or O-L2, or absent when X2 is O; and
L1 and L2 are independently selected from hydrogen and a protecting group independently selected from the group consisting of C1-C12 alkylcarbonyl, C1-C6 alkyl, aryl (C1-C6) alkyl, silyl (C1-C10), carbonate, C1-C6 alkoxy-(C1-C6) alkyl, 3,4-dimethoxybenzyl, p-methoxybenzyl, and C1-C6 ester, or L1 and L2 together are a protecting group selected from the group consisting of pyran, cyclic C1-C6 acetal, cyclic C3-C7 ketal, and cyclic carbonate, provided that when X1 is CN, L1 is absent; or a salt thereof.

US Pat. No. 10,214,537

BICYCLIC HETEROARYL AMINE COMPOUNDS

Bristol-Myers Squibb Comp...

1. A compound of Formula (I):
or a salt thereof; wherein:
X is N or CH;
Q1 is:
(i) Cl, I, —CN, —CH3, —CD3, or —CF3;
(ii) a 5-membered heteroaryl selected from pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, triazolyl, oxadiazolyl, and thiadiazolyl;
(iii) a 6-membered heteroaryl selected from pyridinyl, pyridazinyl, and pyrimidinyl; or
(iv) a bicyclic heteroaryl selected from indolyl, imidazopyridinyl, pyrrolopyridinyl, pyrazolopyridinyl and benzo[d]oxazolyl;
wherein each of said 5-membered, 6-membered, and bicyclic heteroaryls is substituted with zero to 1 Ra and zero to 1 Rb;
Ra is C1-6 alkyl, C1-6 deuteroalkyl, C1-4 fluoroalkyl, C1-4 hydroxyalkyl, C1-4 alkoxyalkyl, C1-4 hydroxyfluoroalkyl, —CH2(C3-6 cycloalkyl), —CH2(oxetanyl), —CH2(methyloxetanyl), —NH2, —S(O)2(C1-4 alkyl), —S(O)2(C3-6 cycloalkyl), C3-6 cycloalkyl, C3-6 fluorocycloalkyl, oxetanyl, tetrahydropyranyl, pyridinyl, pyrimidinyl, pyridazinyl, phenyl, or fluorophenyl substituted with zero to 1 substituent selected from F, —CF3, and —OCF3;
Rb is Cl, C1-4 alkyl, C1-3 haloalkyl, or C3-5 cycloalkyl;
R1 is H or F;
R2 is H or F;
R3 is H or Rx;
R4 is H, F, Cl, —CN, —CH3, —CHF2, —CF3, —OCH3, —OCD3, —(CH2)1-3ORc, —CHRcOH, —C(CH3)2OH, —C(O)OCH3, —C(O)N(Rw)2, —C(O)—NRwR7, —C(O)R8, —C?C—(C1-4 alkyl), —S(O)0-2(C1-4 alkyl), or —S(O)0-2(C3-6 cycloalkyl), or triazolyl, wherein the triazolyl is substituted with 0 to 1-CH3;
Rc is H, —CH3, —CD3, —CH2CH3, —CH(CH3)2, or cyclopropyl;
R5 is H, F, Cl, —CH3, or —OCH3;
R6 is H or F;
R7 is CD3, C1-6alkyl, C1-4haloalkyl, C1-6alkyl substituted with 0-1 R7a, cyclopropyl, cyanoC1-6alkyl, or pyridinyl;
R7a is —CN, —N(Rw)2, —OCH3, or —S(O)2CH3;
R8 is C1-6alkyl, hydroxyC1-6alkyl, morpholinyl, or piperazinyl, wherein the piperazinyl is substituted with 0 to 1-CH3;
Rw is H or —CH3;
Rx is:
(i) C1-4 hydroxyalkyl, C1-4 alkoxyalkyl, C1-4 aminoalkyl, —CRwRwNH(C1-4 alkyl), —CRwRwN(C1-4 alkyl)2, —CRwRwNRw(CH2)1-3O(C1-3 alkyl), —CRwRwCRwRwN(C1-3 alkyl)2, —CRwRwCRwRwNRwC(O)(C1-3 alkyl), —CRwRwC(O)(C1-3 alkyl), —CRwRwNRwC(O)(C1-4 hydroxyalkyl), —(CRwRw)2R3a, —CRw(CF3)R3a, —CRwRwNRwR3a, —CH2NHS(O)2CH3—CH2OR3a, —CH2(8-oxa-3-azabicyclo[3.2.1]octanyl), —CH(CH3)(dimethylazetidinyl), —CH(CH3)(methyl hydroxyazetidinyl), or —CRwRwNRwC(O)R3a, wherein R3a is tetrahydropyran, morpholinyl, morpholinonyl, oxazinanonyl, oxazolidinonyl, pyrrolidinyl, pyrrolidinonyl, piperazinyl, pyridinyl, pyrrolidinium, or phenyl, each substituted with zero to 1 substituent selected from F, Cl, C1-4 alkyl, and —C(O)CH3;
(ii) —C(O)OH or —C(O)R3b, wherein R3b is pyrrolidinyl, pyrrolidinonyl, azetidinyl, morpholinyl, dioxidothiomorpholinyl, thiadiazolyl, piperazinyl, piperazinonyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, or piperidinyl, each substituted with zero to 2 substituents independently selected from F, —OH, —CN, C1-2 alkyl, C1-3 hydroxyalkyl, —C(O)(C1-3 alkyl), —C(O)NRwRw, —C(O)O(C1-3 alkyl), —NRwC(O)(C1-3 alkyl), —C(O)NH(C1-3 hydroxyalkyl), and —C(O)tetrahydrofuranyl; —C(O)NRwRw, —C(O)NH(C1-4 alkyl), —C(O)N(C1-4 alkyl)2, —C(O)NRw(C1-3 fluoroalkyl), —C(O)NRw(C1-3 hydroxyalkyl), —C(O)NRw(C1-4 alkoxyalkyl), —C(O)NRw(CRwRwC(O)NRwRw), —C(O)NRwCRw(C1-4 alkyl)C(O)NRwRw, —C(O)NRw(C1-6 hydroxyalkyl), —C(O)NRwR3c, —C(O)NRw(CRwRw)1-2R3c, —C(O)NRwCRwRwC(O)R3c, —C(O)N(C1-4 alkyl)(C3-6 cycloalkyl), —C(O)N(C3-6 cycloalkyl)2, —C(O)N(C3-6 cycloalkyl)R3c, —C(O)N(C3-6 cycloalkyl)(CH2R3c), or —C(O)CRwRwS(O)2(C1-4 alkyl), wherein R3c is phenyl, oxazolyl, oxopiperidinyl, oxopyrrolidinyl, tetrahydropyranyl, tetrazolyl, thiazolyl, piperidinyl, pyrazolyl, oxetanyl, morpholinyl, pyrrolidinyl, or isoxazolyl, each substituted with zero to 2 substituents independently selected from —CH3, —C(O)CH3, —C(O)NH2, cyclopropyl, and —CH2OH;
(iii) —OR3d wherein R3d is tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, or pyridinyl, each substituted with zero to 3 substituents independently selected from —CH3, ?O, —C(O)CH3, and —C(O)CH(CH3)2;
(iv) —NRwC(O)(C1-3 alkyl), —NRwS(O)2(C1-3 alkyl), or —S(O)2NRwRw;
(v) C3-6 cycloalkyl substituted with zero to 3 substituents independently selected from F, —OH, C1-3 alkyl, C1-3 fluoroalkyl, C1-3 alkoxy, C1-3 fluoroalkoxy, —C(O)NRw(C1-4 alkyl), —C(O)NRw(C1-4 fluoroalkyl), —C(O)NRw(C3-6 cycloalkyl), and —C(O)NRwR3d, wherein R3d is oxetanyl, azetidinyl, morpholinyl, piperidinyl, pyrrolidinyl, cyclobutyl, or tetrahydropyranyl, each substituted with zero to 2 substituents independently selected from F, —CH3, and —OCH3; or
(vi) azetidinyl, oxetanyl, tetrahydropyranyl, piperazinyl, pyrrolidinyl, piperidinyl, 1,2-dihydropyridinonyl, morpholinyl, 4,7-diazaspiro[2.5]octanyl, octahydrobenzo[b] [1,4]oxazinyl, or benzo[b][1,4]oxazinyl, each substituted with zero to 8 substituents independently selected from D, —OH, —CN, C1-4 alkyl, C1-3 deuteroalkyl, C1-3 fluoroalkyl, C1-4 cyanoalkyl, C1-4 hydroxyalkyl, C1-3 alkoxy, ?O, —(CH2)O(O)CH3, —C(O)(C1-4 alkyl), —C(O)(C1-4 hydroxyalkyl), —C(O)NRwRw, —C(O)CH2CN, —C(O)CH2OH, —C(O)(C3-4 cycloalkyl), —C(O)NH2, —S(O)2CH3, —C(O)OCH3, —NHC(O)(C1-4 alkyl), —NRwS(O)(C1-3 alkyl), —NRwS(O)2(C1-3 alkyl), —C(O)CRwRwS(O)2(C1-4 alkyl), —C(O)(phenyl), —C(O)(fluorophenyl), —C(O)(chlorophenyl), —C(O)(hydroxypropyl phenyl), —C(O)(difluorocyclopropyl), —C(O)(oxazolyl), —C(O)(pyrazinyl), —C(O)(pyrazolyl), —C(O)(pyridazinyl), —C(O)(pyridinyl), —C(O)(pyrimidinyl), —C(O)(pyrrolidinyl), —C(O)(tetrahydropyranyl), —C(O)(thiazolyl), —C(O)(methyl thiazolyl), —C(O)(imidazolyl), —C(O)(methyl imidazolyl), —C(O)(methyl oxazolyl), —C(O)(methyl phenyl), —C(O)(methyl pyrazolyl), —C(O)(morpholinyl), —C(O)(acetophenonyl), —C(O)CH2(oxazolidinonyl), —C(O)CH2(pyrrolidinyl), —C(O)CH2(dioxidothiazinanyl), —C(O)CH2(dioxidothiomorpholinyl), —C(O)CH2 (dimethyl-oxopyrrolidinyl), —C(O)CH2 (trimethyl-oxopyrrolidinyl), —C(O)CH2NHC(O)CH3, —C(O)CH2CH2NHC(O)CH3, —C(O)CH2CH2S(O)2CH3, —C(O)CH2S(O)2CH3, —C(O)CH(CH3)S(O)2CH3, —C(O)CH2CH2NHS(O)2CH3, —C(O)CH2NHS(O)2CH3, —C(O)CH2CH2NHS(O)2CH3, —C(O)CH(CH3)NHS(O)2CH3, —C(O)CH2CH2(methyl-pyrazolyl), —N(CH3)2, —N(CH3)(acetyl piperidinyl), —CH2C(O)NHCH2C(CH3)2OH, —N(CH3)C(O)CH3, —N(CH3)C(O)C(CH3)2OH, —N(CH3)C(O)NH(CH(CH3)2), —N(CH3)C(O)(furanyl), —N(CH3)C(O)CH2(pyrazinyl), —N(CH3)C(O)(cyanocyclopropyl), —N(CH3)C(O)CH(CH3)OH, benzyl, carbamoyl azepanyl, carbamoyl-morpholinyl, chlorophenyl, cyclopropyl, cyclobutyl, dioxothiomorpholinyl, fluorobenzoyl, fluorophenyl, hydroxypiperidinyl, hydroxypyrrolidinyl, hydroxytetrahydropyranyl, methoxytetrahydropyranyl, methyl imidazol[1,2a]pyridinyl, methyloxadiazolyl, methylpiperazinyl, methylpiperazinonyl, methyl pyridinonyl, morpholinyl, oxetanyl, phenyl, piperidinonyl, pyridinyl, and pyrimidinyl;
(vii) phenyl, pyrazolyl, dioxothiazinanyl, pyrrolidinonyl, dimethyloxazolindinonyl, oxazolyl, tetrazolyl, pyridinyl, dioxothiomorpholinyl, quinazolinyl, thiazolyl, octahydropyrrolo[3,4-c]pyrrole, 1H-pyrido[1,2-c] pyrimidine-1,3(2H)-dione, 1,3-oxazinan-2-onyl, 1H,2H,3H,4H,6H-pyrido[1,2-a] piperazinone-1,6-dionyl, 2,3-dihydroquinazolin-4(1H)-onyl, methoxy 2,3-dihydroquinazolin-4(1H)-onyl, 2-azaspiro[4.5]decan-3-onyl, 2-oxa-6-azaspiro[3.3]heptanyl, acetyl 3,8-diazabicyclo [3.2.1]octanyl, acetyl-3,4-dihydroquinoxalin-1(2H)-yl, methyl [1,2,4]triazolo[4,3-a]pyridinyl), or dimethyl[1,2,4]triazolo[4,3-a]pyridinyl, each substituted with zero to 4 substituents independently selected from D, F, Cl, —OH, —CN, —NH2, C1-3 alkyl, C1-5 hydroxyalkyl, C1-5 alkoxyalkyl, —C(O)CH3, —C(O)C(CH3)2OH, —C(O)NH2, —C(O)NH(C1-4 alkyl), —CH(Rw)CH2NRwRw, —C(O)NRwRw, —S(O)2NH2, —S(O)2(C1-4 alkyl), —NRwC(O)(C1-4 alkyl), —NRwS(O)0-2(C1-4 alkyl), ?O, C3-6 cycloalkyl, —O(piperidinyl-S(O)2CH3), —O(piperidinyl-C(O)NRw(C1-4 alkyl), and —O(piperidinyl-C(O)(C1-4 hydroxyalkyl);
provided that if R3 is H, then R4 is —C(O)N(CH3)2; and
if Q1 is Br, then R3 is not —CH2OH.

US Pat. No. 10,214,536

AMLEXANOX ANALOGS

THE REGENTS OF THE UNIVER...

1. A composition comprising a compound of Formula (I):
wherein, when M is N, R7 is selected from the group consisting of H, Br, Cl, F, I, D (deuterium), methyl, ethyl, propyl, isopropyl, butyl, CH2F, CH2CH2Cl, CHBrCH3, CF2H, CH2CCl2H, CBr3, CF3, CCl3, CH2CBr3, CH2CF3, CH2CCl3, 1-(trifluoromethyl)cyclopropyl, 1-(trichloromethyl)cyclohexyl, an alkene, an alkyne, NH2, NH-methyl, NH-ethyl, NH—CH2-Ph, (CH2)1-6—NH2(CH2)1-6—NH—(CH2)1-5CH3, (CH2)1-6—N(CH3)2, alkene-N(CH3)2, alkyne-N(CH3)2, N(CH3)2, O-alkyl, NH—(CH2)2-6—OH, OH, (CH2)1-6OH, CH2CHOHCH2OH, cycloalkyl, (CH2)1-6-cycloalkyl, alkene-cycloalkyl, cycloalkene, alkyl-cycloalkenyl, alkene-cycloalkenyl, (CH2)0-6-(non-aromatic heterocycle), and (CH2)0-6-(heteroaryl);
wherein, when M is C, R7 is selected from the group consisting of H, Br, F, I, D (deuterium), CH2F, CH2CH2Cl, CHBrCH3, CF2H, CH2CCl2H, CBr3, CF3, CCl3, CH2CBr3, CH2CF3, CH2CCl3, 1-(trifluoromethyl)cyclopropyl, 1-(trichloromethyl)cyclohexyl, an alkenyl, an alkynyl, NH2, NH-methyl, NH-ethyl, NH—CH2-Ph, (CH2)1-6—NH2(CH2)1-6—NH—(CH2)1-5CH3, (CH2)1-6—N(CH3)2, alkenyl-N(CH3)2, alkynyl-N(CH3)2, NH—(CH2)2-6—OH, OH, (CH2)1-6OH, CH2CHOHCH2OH, cycloalkyl, (CH2)1-6-cycloalkyl, alkenyl-cycloalkyl, cycloalkenyl, alkyl-cycloalkenyl, alkenyl-cycloalkenyl, (CH2)0-6-(non-aromatic heterocycle), and (CH2)0-6-(heteroaryl); wherein, when M is C, R7 is not (CH2)2-cyclohexyl;
wherein, when M is C, and R7 is H or D, R8 is selected from the group consisting of Br, Cl, F, I, D (deuterium), methyl, ethyl, propyl, isopropyl, butyl, CH2F, CH2CH2Cl, CHBrCH3, CF2H, CH2CCl2H, CBr3, CF3, CCl3, CH2CBr3, CH2CF3, CH2CCl3, 1-(trifluoromethyl)cyclopropyl, 1-(trichloromethyl)cyclohexyl, an alkene, an alkyne, NH2, NH-methyl, NH-ethyl, NH—CH2-Ph, (CH2)1-6—NH2, CH2)1-6—NH—(CH2)1-5CH3, (CH2)1-6—N(CH3)2, alkenyl-N(CH3)2, alkynyl-N(CH3)2, N(CH3)2, O-alkyl, NH—(CH2)2-6—OH, (CH2)1-6OH, CH2CHOHCH2OH, cycloalkyl, (CH2)1-6-cycloalkyl, alkenyl-cycloalkyl, cycloalkenyl, alkyl-cycloalkenyl, alkenyl-cycloalkenyl, (CH2)0-6-(non-aromatic heterocycle), and (CH2)0-6-(heteroaryl),
wherein, when M is C, and R7 is not H or D, R8 is H, F, or D; and
wherein R8 is absent if M is N.

US Pat. No. 10,214,535

HYDROXMETHYL PIPERIDINE OREXIN RECEPTOR ANTAGONISTS

1. A compound of the formula Ia:
wherein:
R1a, R1b and R1c are independently selected from the group consisting of:
(1) hydrogen,
(2) halogen,
(3) hydroxyl,
(4) C1-6alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(5) —O—C1-6alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,
(6) —CN, and
(7) heteroaryl, wherein heteroaryl is selected from imidazolyl, indolyl, oxazolyl, pyridyl, pyrrolyl, pyrimidinyl, tetrazolyl, and triazolyl, which is unsubstituted or substituted with halogen, hydroxyl, C1-6alkyl, —O—C1-6alkyl or —NO2;
R2 is hydrogen or methyl;
R3 is hydrogen or methyl;
R5 is selected from the group consisting of: hydrogen, fluoro, methyl, and methoxy;
R6 is selected from the group consisting of: —CN, methyl, methoxy, and difluoroethoxy;
or a pharmaceutically acceptable salt thereof.

US Pat. No. 10,214,534

SUBSTITUTED 2-PHENYL (AZA)BENZOFURAN COMPOUNDS FOR THE TREATMENT OF HEPATITIS C

Bristol-Myers Squibb Comp...

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof:
wherein
X is N or C—R10;
R1 is methyl;
R2 is OAr1;
Ar1 is phenyl or pyridinyl and is substituted with 0-3 substituents selected from the group of cyano, halo, alkyl, cycloalkyl, haloalkyl, hydroxy, alkoxy, and haloalkoxy;
R3 is hydrogen, halo, or alkyl;
R4, R5, R6, R7, R8 are each independently selected from the group of hydrogen, halo, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, hydroxyalkyl, hydroxycycloalkyl, alkoxyalkyl, alkoxycycloalkyl, alkoxy, hydroxyalkyloxy, alkoxyalkyloxy, and CON(R202)(R203);
R202 and R203 are each independently selected from the group of hydrogen, alkyl, and cycloalkyl;
R9 is selected from the group of haloalkyl and NR301R302;
R301 is selected from the group of hydrogen, alkyl, cycloalkyl, (cycloalkyl)alkyl, benzyl, alkylcarbonyl, haloalkylcarbonyl, alkyl sulfonyl, phenyl sulfonyl, (alkoxyphenyl)sulfonyl and (haloalkoxyphenyl)sulfonyl;
R302 is hydrogen, alkyl, hydroxyalkyl, or alkoxyalkyl; and
R10 is hydrogen.

US Pat. No. 10,214,533

N-ACYL-(3-SUBSTITUTED)-5,6,7,8-TETRAHYDRO-[1,2,4]TRIAZOLO[4,3-A]PYRAZINES AS SELECTIVE NK-3 RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITION, METHODS FOR USE IN NK-3 RECEPTOR-MEDIATED DISORDERS

OGEDA SA, Charleroi (BE)...

1. A process of manufacturing a compound of Formula I:
or a pharmaceutically acceptable solvate thereof, wherein:
R1 is H or F;
R1? is H;
R2 is H, F or Cl;
R2? is H or F;
R3 is F or Cl;
R4 is methyl, trifluoromethyl, difluoromethyl or fluoromethyl;
X1 is N and X2 is S; or X1 is S and X2 is N; and
represents a single or a double bond depending on X1 and X2;
comprising the following steps:
a) reacting a compound of Formula (i)

wherein:
PG represents a suitable protecting group;
with a compound of Formula (ii)

wherein:
R4? is R4 as defined above or H;
X1 and X2 are as defined above;
represents a single or a double bond depending on X1 and X2;
so as to obtain a compound of Formula (iii)

wherein PG, R4?, X1 and X2 are as defined above and
represents a single or a double bond depending on X1 and X2;
b) deprotecting compound of Formula (iii) with a suitable deprotection agent to afford compound of Formula (iv)

wherein R4?, X1 and X2 are as defined above and
represents a single or a double bond depending on X1 and X2;
c) when R4? is H, a trifluoromethyl or difluoromethyl group is introduced by direct C—H trifluoro- or difluoromethylation, leading to compound of Formula (v)

wherein X1 and X2 are as defined above and R4 is trifluoromethyl, or difluoromethyl and represents a single or a double bond depending on X1 and X2;
d) N-acylating compound of Formula (iv) wherein R4? is not H or compound of Formula (v) with a compound of Formula (vi)

wherein R1, R1?, R2, R2? and R3 are as defined above;
to afford compound of Formula I as defined above.

US Pat. No. 10,214,532

PROCESS FOR PREPARING IBRUTINIB

Shanghai Dude Medical Sci...

1. A process for preparing ibrutinib, comprisingStep 1: reacting a compound of Formula 1 with a compound of Formula 4 in the presence of a base and a catalyst to produce a compound of Formula 8,

Step 2: reacting the compound of Formula 8 with a compound of Formula 2-1 in the presence of a base to produce ibrutinib,

wherein X1 is independently selected from the group consisting of Cl, Br and I; X2 is independently selected from the group consisting of Cl and Br.

US Pat. No. 10,214,531

SUBSTITUTED AMINO TRIAZOLES, AND METHODS USING SAME

Institute for Drug Discov...

1. A compound of formula (I), or a salt, hydrate or solvate thereof:
wherein in (I):
m is 0, 1, 2, 3, or 4;
n is 0, 1, or 2;
R1 is aryl or heteroaryl, each of which is optionally substituted with one or more of R4;
each R2 is individually selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, hydroxy(C1-C6 alkyl), C1-C6 acyloxy(C1-C6 alkyl), alkoxy(C1-C6 alkyl), and C1-C6 haloalkoxy;
R3 is a substituent on one nitrogen atom, and is hydrogen or C1-C6 alkyl;
W is absent, —O—, —N(R5)—, —X1—N(R5)—, —X1—O—, —N(R5)C(?O)—, —C(?O)N(R5)—, —N(R5)S(?O)2—, or —S(?O)2N(R5)—, where X1 is C1-C3 alkylene optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —SH, —S(C1-C6 alkyl), hydroxy(C1-C6 alkyl), alkoxy(C1-C6 alkyl), amino(C1-C6 alkyl), —C(?O)NH2, —C(?O)N(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —C(?O)O(C1-C6 alkyl), —NHC(?O)(C1-C6 alkoxy), and —NHC(?O)(C1-C6 alkyl);
X is —C(?O)— or C1-C6 alkylene optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, C1-C6 haloalkyl, benzyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —SH, —S(C1-C6 alkyl), hydroxy(C1-C6 alkyl), alkoxy(C1-C6 alkyl), amino(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —C(?O)O(C1-C6 alkyl), —NHC(?O)(C1-C6 alkoxy), and —NHC(?O)(C1-C6 alkyl);
Y is absent, —C(?O)—, —OC(?O)—, —N(R5), —N(R5)C(?O)—, —C(?O)N(R5)—, —N(R5)S(?O)2—, —S(?O)2N(R5)—, —N(R5)CH2—, or —S(?O)2—;
or W—X—Y represent a heteroarylene, heterocyclylene, or C3-C8 cycloalkylene, each optionally substituted with one or more substituents selected from the group consisting of C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, and C1-C6 haloalkoxy;
Z is CH, C(C1-C6 alkyl), or N, wherein the C1-C6 alkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —SH, —S(C1-C6 alkyl), hydroxy(C1-C6 alkyl), alkoxy(C1-C6 alkyl), amino(C1-C6 alkyl), —C(?O)NH2, —C(?O)N(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —C(?O)O(C1-C6 alkyl), —NHC(?O)(C1-C6 alkoxy), and —NHC(?O)(C1-C6 alkyl);
or Y—Z, together with one carbon atom to which Z is attached, form a heterocyclyl;
or Y—Z, together with the ring containing Z, form a bicyclic heterocycle selected from the group consisting of:

 wherein the N labelled as (a) is covalently bonded to X and the N labelled as (b) is covalently bonded to the 1,3,4-triazole ring;
or Y is absent, X is a bond or as defined above, and Z is a carbon atom that is covalently connected to W by a C1-C4 alkylene chain optionally containing a nitrogen, oxygen, or sulfur atom, whereby Z—X—Y—W together form a 3-7 membered carbocyclic or heterocyclic ring;
each R4 is independently selected from the group consisting of halogen, —NO2, —CN, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —OH, C1-C6 alkoxy, C1-C6 haloalkoxy, —SH, —S(?O)0-2(C1-C6 alkyl), hydroxy(C1-C6 alkyl), alkoxy(C1-C6 alkyl), amino(C1-C6 alkyl), —C(?O)NH2, —C(?O)NH(C1-C6 alkyl), —C(?O)N(C1-C6 alkyl)2, —C(?O)NHNH2, —C(?O)H, —C(?O)O(C1-C6 alkyl), —OC(?O)(C1-C6 alkyl), —NHC(?O)(C1-C6 alkoxy), —NHC(?O)(C1-C6 alkyl), —NHC(?O)NH2, —NHC(?O)NH(C1-C6 alkyl), —NHC(?NH)NH2, —NH—S(?O)0-2—(C1-C6 alkyl), —NH—S(?O)0-2-aryl, and —NH—S(?O)0-2-heteroaryl; and,
each R5 is independently selected from the group consisting of hydrogen and C1-C6 alkyl optionally substituted with at least one substituent selected from the group consisting of halogen, hydroxy, C1-C6 haloalkyl, C3-C7 cycloalkyl, C1-C6 alkoxy, and R5a,
where R5a is phenyl, naphthyl, or a bicyclic heteroaryl, and R5a is optionally substituted with 1-3 substituents independently selected from the group consisting of halogen, hydroxy, C1-C6 alkyl, cyano, hydroxy C1-C6 alkyl, phenyl, C1-C6 alkoxy, haloalkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, and C1-C6 haloalkoxy;
provided the compound of formula (I) is not:
5-[4-(1-naphthalenylmethyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(1,3-benzodioxol-5-ylmethyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(1-phenylethyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[[2-chloro-4-(dimethylamino)phenyl]methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[[3-bromo-4-(dimethylamino)phenyl]methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(2,3,4-trimethoxyphenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(2-chloro-4-fluorophenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[[3-(trifluoromethyl)phenyl]methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(2,4,6-trimethylphenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(2,5-dimethylphenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(2,6-dichlorophenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(2-phenoxyethyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(4-phenoxybutyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[2-(4-bromophenoxy)ethyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(3,4-dichlorophenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(4-pyridinylmethyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(4-methylphenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(phenylmethyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(4-aminophenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[[3-chloro-4-(dimethylamino)phenyl]methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(3-chlorophenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[[2-bromo-4-(dimethylamino)phenyl]methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(3-phenylpropyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[[4-(dimethylamino)phenyl]methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(2-furanylmethyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(2-quinolinylmethyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
4-[[4-(3-amino-1H-1,2,4-triazol-5-yl)-1-piperazinyl]methyl]-benzonitrile;
5-[4-[(2-fluorophenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(2-phenylethyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(4-fluorophenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(2-nitrophenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-(3-phenoxypropyl)-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[[4-(1,1-dimethylethyl)phenyl]methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(4-butylphenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
5-[4-[(3-methylphenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine;
benzyl 4-(3-amino-1H-1,2,4-triazol-5-yl)piperazine-1-carboxylate;
5-[4-[(3,4,5-trimethoxyphenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine; or
5-[4-[(2-methylphenyl)methyl]-1-piperazinyl]-1H-1,2,4-triazol-3-amine.

US Pat. No. 10,214,530

XANTHINE DERIVATIVES, THEIR USE AS A MEDICAMENT, AND PHARMACEUTICAL PREPARATIONS COMPRISING THE SAME

1. A xanthine derivative defined by chemical Formula I or a salt thereof:
wherein R1 and R2 are each an optionally substituted group independently selected from hydrogen (—H), (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-alkynyl, (C5-C14)-aryl, (C5-C14)-heteroaryl, (C6-C15)-alkyl-aryl, (C6-C15)-alkyl-heteroaryl, (C6-C15)-alkenyl-aryl, (C6-C15)-alkenyl-heteroaryl, (C6-C15)-alkynyl-aryl, (C6-C15)-alkynyl-heteroaryl, (C6-C15)-aryl-alkylene, (C6-C15)-heteroaryl-alkylene, (C6-C15)-aryl-alkenylene, (C6-C15)-heteroaryl-alkenylene, (C6-C15)-aryl-alkylylene and (C6-C15)-heteroaryl-alkylylene,
wherein the alkyl, alkenyl, alkynyl, alkylene, alkylene and alkenylene groups optionally comprise one or more bivalent groups substituting a carbon moiety in their hydrocarbon chain and selected from —O—, —S—, —S(O)—, —SO2—, —N?, —N(R)—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)N(R)—, —N(R)C(O)—, —OC(O)N(R)—, —N(R)C(O)O—, —N(R)C(O)N(R)—, (C3-C12)-heterocyclic alkylene and (C3-C12)-heterocyclic alkenylene;
R3 means a number of n groups independently selected from hydrogen (—H), fluoro (—F), bromo (—Br), chloro (—Cl), hydroxyl (—OH), carbonyl (—C(O)R), carboxyl (—C(O)OH), carboxy ester (—CO2R), alkoxy (—OR), aldehyde (—C(O)H), trihalide methyl ester (—OCX3), primary, secondary and tertiary amine (—NR(R?)), amide (—N(R)—C(O)—R), imide (—C(O)—N(R)—C(O)—R?), carbamate (—N(R)—C(O)—OR?), carboxamide (—C(O)N(R)R?), carbimide (—N(R)—C(O)—N(R?)R?), primary and secondary ketimine (—(R)?NR?), secondary ketimine (—(R)?NH), nitrile (—CN), isonitrile (—NC), nitroxy (—ONO), nitro (—NO2), nitrate (—ONO2), nitroso (—NO), cyanate (—OCN), isocyanate (—NCO), sulfhydryl (—SH), sulfide (—SR), sulfurtrihalide (—SX3), sulfurpentahalide (—SX5), sulfinyl (—S(O)R), sulfonyl (—SO2R), sulfino (—SO2H), and sulfo (—SO3H),
and an optionally substituted and optionally linked group selected from (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-alkynyl, (C5-C14)-aryl, (C5-C14)-heteroaryl, (C6-C15)-alkyl-aryl, (C6-C15)-alkyl-heteroaryl, (C6-C15)-alkenyl-aryl, (C6-C15)-alkenyl-heteroaryl, (C6-C15)-alkynyl-aryl, (C6-C15)-alkynyl-heteroaryl, (C6-C15)-aryl-alkylene, (C6-C15)-heteroaryl-alkylene, (C6-C15)-aryl-alkenylene, (C6-C15)-heteroaryl-alkenylene, (C6-C15)-aryl-alkylylene and (C6-C15)-heteroaryl-alkylylene,
wherein the alkyl, alkenyl, alkynyl, alkylene, alkylene and alkenylene groups optionally comprise one or more bivalent groups substituting a carbon moiety in their hydrocarbon chain and selected from —O—, —S—, —S(O)—, —SO2—, —N?, —N(R)—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)N(R)—, —N(R)C(O)—, —OC(O)N(R)—, —N(R)C(O)O—, —N(R)C(O)N(R)—, (C3-C12)-heterocyclic alkylene or (C3-C12)-heterocyclic alkenylene;
Q is selected from methylene (—C(R)H—) and amino (—N(R)—);
X is selected from carbon (—C—) and nitrogen (—N—);
Z is selected from amino (—NH—), oxygen (—O—) and sulfur (—S—); and
n is a number selected from 1, 2 and 3;
wherein in the aforementioned definitions R, R? and R? independently mean hydrogen, (C1-C3)-alkyl or (C2-C3)-alkenyl.

US Pat. No. 10,214,529

SMALL MOLECULES FOR THE TREATMENT OF PRIMARY CANCER AND CANCER METASTASIS

THE BOARD OF REGENTS OF T...

1. A compound that is a chemical analog of non-hydrolysable adenosine ATP analog 5?-[?-thio]triphosphate (ATP?S) with general formula of Formula I:where R1 and R2 are independently selected from hydrogen, cyano, C1 to C3 alkyl, halo, or heteromethyl.

US Pat. No. 10,214,528

BICYCLIC HETEROCYCLES AS FGFR4 INHIBITORS

Incyte Corporation, Wilm...

1. A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
X1 is CR10R11;
X is N or CR6;
R1 is C1-3 alkyl or C1-3 haloalkyl;
R2 is H, halo, C1-3 alkyl, C1-3 haloalkyl, CN, or C1-3 alkoxy;
R3 is H, halo, C1-3 alkyl, C1-3 haloalkyl, CN, or C1-3 alkoxy;
R4 is C1-3 alkyl or C1-3 haloalkyl;
R5 is H, halo, C1-3 alkyl, C1-3 haloalkyl, CN, or C1-3 alkoxy;
R6 is selected from H, halo, CN, ORa4, SRa4, C(O)NRc4Rd4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R6 are each optionally substituted with 1, 2, or 3 substituents independently selected from R10A;
L is —(CR13R14)n—, wherein R13 and R14 are each independently H;
the subscript n is 1 or 2;
R8 is H;
R10 and R11 are each independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, a 5-10 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-10 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl groups of R10 and R11 are each optionally substituted with 1, 2, 3, or 4 R10A;
R10A, at each occurrence, is independently selected from halo, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, C(?NRe4)NRc4Rd4, NRc4C(?NRe4)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl group of R10A are each optionally substituted with 1, 2, or 3 substituents independently selected from R19;
Ra4, Rb4, Rc4, and Rd4, at each occurrence, are independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl group of Ra4, Rb4, Rc4, and Rd4 are each optionally substituted with 1, 2, or 3 substituents independently selected from R19;
alternatively, Rc4 and Rd4 together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group which is optionally substituted with 1, 2 or 3 substituents independently selected from R19;
Re4, at each occurrence, is H or C1-4 alkyl;
alternatively, R10 and R11 together with the carbon atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl group or a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocycloalkyl group; wherein said 3-, 4-, 5-, 6-, or 7-membered cycloalkyl group and 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocycloalkyl group are each optionally substituted with 1, 2, 3 or 4 R10A;
R12 is H or C1-4 alkyl which is optionally substituted by R17;
R17, at each occurrence, is independently selected from halo, CN, NO2, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, C(?NRe7)NRc7Rd7, NRc7C(?NRe7)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)ORa7, NRc7C(O)NRc7Rd7, NRc7S(O)Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, S(O)2NRc7Rd7, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of R17 are each optionally substituted with 1, 2, or 3 substituents independently selected from R19;
Ra7, Rb7, Rc7, and Rd7, at each occurrence, are independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, phenyl, C3-6 cycloalkyl, a 5-6 membered heteroaryl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S, and a 4-7 membered heterocycloalkyl moiety having carbon and 1, 2, or 3 heteroatoms independently selected from N, O and S; wherein said C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl groups of Ra7, Rb7, Rc7, and Rd7 are each optionally substituted with 1, 2, or 3 substituents independently selected from R19;
alternatively, Rc7 and Rd7 together with the nitrogen atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group which is optionally substituted with 1, 2 or 3 substituents independently selected from R19;
Re7, at each occurrence, is independently H or C1-4 alkyl;
R19, at each occurrence, is independently selected from halo, CN, NO2, ORa9, SRa9, C(O)Rb9, C(O)NRc9Rd9, C(O)ORa9, OC(O)Rb9, OC(O)NRc9Rd9, NRc9Rd9, NRc9C(O)Rb9, NRc9C(O)ORa9, NRc9C(O)NRc9Rd9, NRc9S(O)Rb9, NRc9S(O)2Rb9, NRc9S(O)2NRc9Rd9, S(O)Rb9, S(O)NRc9Rd9, S(O)2Rb9, S(O)2NRc9Rd9, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, and C1-4 haloalkyl;
Ra9, Rc9, and Rd9, at each occurrence, are independently selected from H and C1-4 alkyl; and
Rb9, at each occurrence, is independently C1-4 alkyl.

US Pat. No. 10,214,527

TRIAZOLOPYRIDINE INHIBITORS OF MYELOPEROXIDASE

Bristol-Myers Squibb Comp...

1. The compound of the formula
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, or a solvate thereof, wherein:
ring A is independently selected from: phenyl, naphthyl and a 6-membered heteroaryl comprising carbon atoms and 1 to 2 nitrogen atoms; wherein each ring moiety is substituted with 0-1 R2 and 0-3 R3;
R2 is independently selected from: halogen, C1-4 alkyl substituted with 0-1 OH, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, CN, CO2(C1-4 alkyl), SO2(C1-4 alkyl), —(CH2)n(X1)n(CH2)nR4, and —(CH2)nCONH(CH2)mR4;
X1 is independently selected from: O, CO, NR1 and S(O)p;
R1 is independently selected from: H and C1-4 alkyl;
R3 is, independently at each occurrence, selected from: OH, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy;
alternatively, when R2 and one of the R3s are attached to two adjacent carbon atoms of ring A selected from phenyl and pyridyl, they can be combined with the two attached carbon atoms to form a 5- to 6-membered carbocycle or heterocycle comprising carbon atoms and 0-3 additional heteroatoms selected from N, NRb, 0, and S(O)p, wherein said carbocycle or heterocycle is substituted with 0-2 Ra;
R4 is independently at each occurrence selected from: C3-6 cycloalkyl substituted with 0-3 Rc, phenyl substituted with 0-4 Rc, and 5- to 10-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NRb, O, and S; wherein said heterocycle is substituted with 0-3 Rc;
Ra is, independently at each occurrence, selected from: OH, CN, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy;
Rb is, independently at each occurrence, selected from: H, C1-4 alkyl, C1-4 haloalkyl, CO(C1-4 alkyl), CO2(C1-4 alkyl), SO2(C1-4 alkyl, —(CH2)t-phenyl substituted with 0-1 Rd;
Rc is, independently at each occurrence, selected from: OH, halogen, C1-6 alkyl substituted with 0-1 OH, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, CN, CONH2, CONH(C1-4 alkyl), CON(C1-4 alkyl)2, —(O)n(CH2)t—C3-6 carbocycle, —(CH2)t(O)n(C3-6 carbocycle), and —(CH2)t-(5- to 6-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NRb, O, and S); wherein said carbocycle and heterocycle are substituted with 0-2 Rd;
Rd is independently at each occurrence, selected from the group consisting of halogen, C1-4 alkyl substituted with 0-1 OH, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, CN, —(CH2)t(O)n—(C3-6 carbocycle) and —(O)n(CH2)t—(C3-6 carbocycle);
m is, independently at each occurrence, selected from 1, 2 and 3;
n is, independently at each occurrence, selected from 0 and 1;
p is, independently at each occurrence, selected from 0, 1 and 2; and
t is, independently at each occurrence, selected from 0, 1, 2, and 3.

US Pat. No. 10,214,526

SUBSTITUTED PYRAZOLO[1,5-A]-PYRIDINE-3-CARBOXAMIDES AND USE THEREOF

Bayer Pharma Aktiengesell...

9. A medicament comprising the compound as defined in claim 1 in combination with one or more inert, nontoxic, pharmaceutically suitable excipients.

US Pat. No. 10,214,525

CHLORINATED NAPTHALENETETRACARBOXYLIC ACID DERIVATIVES, PREPARATION THEREOF AND USE THEREOF IN ORGANIC ELECTRONICS

BASF SE, Ludwigshafen (D...

1. A compound of the formula (I.Ba)
in which
R1 and R3 are each Cl and R2 and R4 are each hydrogen, or
R1 and R4 are each Cl and R2 and R3 are each hydrogen,
Ra and Rb are each independently 1H,1H-perfluoro-C2-C30-alkyl or 1H,1H,2H,2H-perfluoro-C3-C30-alkyl, wherein Ra and Rb are not each 1H,1H-perfluoro-C4-alkyl.

US Pat. No. 10,214,524

2-HETEROARYL CARBOXAMIDES

BAYER INTELLECTUAL PROPER...

1. A compound of the formula
for the treatment of Alzheimer's disease or schizophrenia, wherein
R1 is 1-azabicyclo[2.2.2]oct-3-yl, which is optionally substituted via the nitrogen atom by a radical selected from the group of C1-C4-alkyl, benzyl and oxy,
R2 is hydrogen or C1-C6-alkyl,
R3 is hydrogen, halogen or C1-C6-alkyl,
R4 is hydrogen, halogen, cyano, amino, trifluoromethyl, trifluoromethoxy, C1-C6-alkyl, C1-C6-alkylcarbonyl, C1-C6-alkylamino, formyl, hydroxycarbonyl, C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C1-C6-alkylthio, C1-C6-alkylcarbonylamino, C1-C6-alkylaminocarbonyl, C1-C4-alkylsulphonylamino, C3-C8-cycloalkylcarbonylamino, C3-C6-cycloalkylaminocarbonyl, pyrrolyl, C1-C6-alkylaminocarbonylamino, heterocyclylcarbonyl, heterocyclylcarbonylamino, heteroarylcarbonylamino, hydroxyl, phenyl or heterocyclyl,
wherein C1-C6-alkyl is optionally substituted by hydroxyl, cyano, amino, C1-C6-alkylaminocarbonylamino, C1-C6-alkylaminocarboxyl, heterocyclyl or aryl, C1-C6-alkylaminocarbonyl is optionally substituted by C1-C6-alkoxy or C1-C6-alkylamino, C1-C6-alkylcarbonylamino is optionally substituted by C1-C6-alkoxy, and heterocyclyl is optionally substituted by oxo,
A is oxygen or sulphur,
the ring B is benzo, optionally substituted by radicals from the series halogen, cyano, formyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C1-C6-alkyl and C1-C6-alkoxy,
and
E is C?C, arylene and heteroarylene, wherein arylene and heteroarylene are optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C1-C6-alkoxy and C1-C6-alkyl,
or a solvate, a salt or a solvate of a salt thereof.

US Pat. No. 10,214,523

PRODUCTION METHOD OF THIAZOLE DERIVATIVE

KYOWA HAKKO KIRIN CO., LT...

1. A production method of a compound represented by formula (C), comprising a step (i) of reacting a compound represented by formula (A) and a compound represented by formula (B):
where R1 represents furyl, R4, R5 and R6 independently represent lower alkyl or aryl, R2 represents pyridyl or tetrahydropyranyl, and X1 represents halogen.

US Pat. No. 10,214,522

ANTI-ALPHAVBETA1 INTEGRIN INHIBITORS AND METHODS OF USE

The Regents of the Univer...

1. A method for treating fibrosis, said method comprising administering to a subject in need thereof an effective amount of a compound, or a salt thereof, having the formula:
wherein,
Ring A is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
Ring C is aryl or heteroaryl;
L2 is independently a bond or substituted, unsubstituted C1-C10 alkylene, or unsubstituted 2 to 10 membered heteroalkylene;
L3 is a bond, substituted or unsubstituted C1-C10 alkylene, substituted or unsubstituted 2 to 10 membered heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or substituted or unsubstituted alkylarylene;
Y is —C(O)N(R4)—, —O—, —C(O)O—, —S—, —N(SO2R4)—, —N(C(O)R4)—, —N(C(O)OR4)—, —N(R4)C(O)—, —N(R4)—, —N(R4)C(O)NH—, —NHC(O)N(R4)—, —N(R4)C(O)O—, —C(O)—, —N(R4)CH2—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, or substituted or unsubstituted arylene;
R1 is independently halogen, —N3, —CX3, —CHX2, —CH2X, —CN, —CHO, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2, —SO2CH3 —SO3H, —OSO3H, —SO2NH2, —SO2Ph, —NHNH2, —ONH2, —NHC(O)NHNH2, —OPO3H, —PO3H2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a detectable moiety;
R2 is —NR3AR3B, —C(NH)NH2, —C(NH)R3B, —C(NR3A)NH2, —C(NR3A)R3B, —C(NCN)NH2, —NH2, —C(NH)NHR3B, —C(NR3A)NHR3B, —C(NCN)NHR3B, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted fused ring cycloalkyl, substituted or unsubstituted fused ring heterocycloalkyl, substituted or unsubstituted fused ring aryl, or substituted or unsubstituted fused ring heteroaryl;
R3A and R3B are independently hydrogen, —C(NH)NH2, —C(NH)R3D, —C(NR3C)NH2, —C(NR3C)R3D, —C(NCN)NH2, —NH2, —C(NH)NHR3D, —C(NR3C)NHR3D, —C(NCN)NHR3D, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, wherein R3A and R3B are optionally joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl;
R3C is hydrogen, halogen, —N3, —CX1C3, —CHX1C2, —CH2X1C, —CN, —CHO, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2, —SO2CH3 —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R3D is hydrogen, halogen, —N3, —CX1D3, —CHX1D2, —CH2X1D, —CN, —CHO, —OH, —NH2, —COOH, —CONH2, —NO2, —SH, —SO2, —SO2CH3 —SO3H, —SO4H, —SO2NH2, —NHNH2, —ONH2, —NHC(O)NHNH2, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R4 is hydrogen or unsubstituted C1-C5 alkyl;
R12 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or a prodrug moiety;
each X, X1C and X1D is independently —F, —Cl, —Br, or —I; and
z1 is an integer from 0 to 5.

US Pat. No. 10,214,521

FUSED HETEROCYCLIC COMPOUNDS AS GPR120 AGONISTS

Piramal Enterprises Limit...

1. A compound of formula (I);
wherein,
X1 is —O—;
X2 is —CR?—;
Ring A is (C6-C10)aryl;
Ring B is (C6-C10)aryl, 5- to 10-membered heteroaryl or a saturated or partially unsaturated 3- to 11-membered heterocyclyl ring containing one to four heteroatoms independently selected from the group consisting of O, N and S;
R1 is hydrogen or (C1-C6)alkyl;
R2 at each occurrence is independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, nitro, —NR5R6, —C(O)R5, —C(O)NR5R6, —S(O)tR7, (C1-C6)alkyl, halo(C1-C6)alkyl, —O(C1-C6)alkyl and (C6-C10)aryl;
R3 and R4 at each occurrence are independently selected from the group consisting of hydrogen, halogen, oxo, cyano, nitro, —NR5R6, —C(O)R5, —C(O)NR5R6, —S(O)tR7, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy, —O(C1-C6)alkyl, (C3-C8)cycloalkyl, (C6-C10)aryl, —O(C6-C10)aryl, heterocyclyl and heteroaryl;
R5 and R6 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C6-C10)aryl, heterocyclyl and heteroaryl;
R7 is hydrogen, (C1-C6)alkyl or —NR5R6;
R? is selected from the group consisting of hydrogen, (C1-C6)alkyl, —C(O)(C1-C6)alkyl, —C(O)O(C1-C6)alkyl and —S(O)2(C1-C6)alkyl;
Ra and Rb at each occurrence are independently selected from the group consisting of hydrogen, halogen and (C1-C6)alkyl;
n is 3;
p is an integer from 1 to 3;
q is an integer from 1 to 4;
t is an integer from 0 to 2;
------- represents a single bond;
wherein,
(C1-C6)alkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro, —NR5R6, —C(O)R5, —C(O)NR5R6, —S(O)tR7, (C1-C6)alkyl, halo(C1-C6)alkyl, —O(C1-C6)alkyl, (C3-C8)cycloalkyl, (C6-C10)aryl, heterocyclyl and heteroaryl; wherein R5, R6, R7 and t are as defined above;
—O(C1-C6)alkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro, —NR5R6, —C(O)R5, —C(O)NR5R6, —S(O)tR7, (C1-C6)alkyl, halo(C1-C6)alkyl, (C3-C8)cycloalkyl, (C6-C10)aryl and heterocyclyl; wherein R5, R6, R7 and t are as defined above;
(C3-C8)cycloalkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of oxo, halogen, hydroxy, cyano, nitro, —NR5R6, —C(O)R5, —C(O)NR5R6, —S(O)tR7, (C1-C6)alkyl, halo(C1-C6)alkyl and —O(C1-C6)alkyl; wherein R5, R6, R7 and t are as defined above;
(C5-C8)cycloalkenyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro, —NR5R6, —C(O)R5, —C(O)NR5R6, —S(O)tR7, (C1-C6)alkyl, halo(C1-C6)alkyl and —O(C1-C6)alkyl; wherein R5, R6, R7 and t are as defined above;
(C6-C10)aryl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro,
—C(O)R5, —C(O)OR5, —S(O)tR7, —NR5R6, (C1-C6)alkyl, halo(C1-C6)alkyl, —O(C1-C6)alkyl, halo(C1-C6)alkoxy, (C3-C8)cycloalkyl, (C6-C10)aryl, —O(C6-C10)aryl, heterocyclyl and heteroaryl, wherein R5, R6, R7 and t are as defined above;
heterocyclyl is a 3- to 11-membered ring, which is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro, —C(O)R5, —C(O)OR5, —S(O)tR7, —NR5R6, (C1-C6)alkyl, halo(C1-C6)alkyl, —O(C1-C6)alkyl, halo(C1-C6)alkoxy, (C3-C8)cycloalkyl, (C6-C10)aryl, heterocyclyl and heteroaryl; wherein R5, R6, R7 and t are as defined above;
heteroaryl is a 5- to 10-membered ring, which is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro, —C(O)R5, —C(O)OR5, —S(O)tR7, —NR5R6, (C1-C6)alkyl, halo(C1-C6)alkyl, —O(C1-C6)alkyl, halo(C1-C6)alkoxy, (C3-C8)cycloalkyl, (C6-C10)aryl, heterocyclyl and heteroaryl; wherein R5, R6, R7 and t are as defined above;
halogen is chlorine, bromine, iodine or fluorine;
or an isotopic form, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, N-oxide, S-oxide, or a carboxylic acid isostere thereof, wherein the carboxylic acid isostere is selected from:
wherein R is hydrogen or (C1-C3)alkyl.

US Pat. No. 10,214,520

SUBSTITUTED AZASPIRO(4.5)DECANE DERIVATIVES

GRUENENTHAL GMBH, Aachen...

1. A compound of the general formula (1)
wherein
Y1, Y1?, Y2?, Y2?, Y3, Y3?, Y4 and Y4? in each case independently of each other are chosen from the group consisting of —H, —F, —Cl, —Br, —I, —CN, —NO2, —CHO, —R0, —C(?O)R0, —C(?O)H, —C(?O)—OH, —C(?O)OR0, —C(?O)NH2, —C(?O)NHR0, —C(?O)N(R0)2, —OH, —OR0, —OC(?O)H, —OC(?O)R0, —OC(?O)OR0, —OC(?O)NHR0, —OC(?O)N(R0)2, —SH, —SR0, —SO3H, —S(?O)1-2—R0, —S(?O)1-2NH2, —S(?O)1-2—NHR0, —S(?O)1-2—N(R0)2, —NH2, —NHR0, —N(R0)2, —N+(R0)3, —N+(R0)2O?, —NHC(?O)R0, —NHC(?O)OR0, —NHC(?O)NH2, —NHC(?O)NHR0 and —NHC(?O)N(R0)2; or Y1 and Y1?, or Y2 and Y2?, or Y3 and Y3?, or Y4 and Y4? together represent ?O;
X1, X1?, X2, X2?, X3 and X3 in each case independently of each other represent —H, —F, —Cl, —Br, —I, —NO2, —CF3, —OR5, —SR5, —SO2R5, —S(?O)2OR5, —CN, —COOR5, —CONR5, —NR6R7, or —R0; or X1 and X1?, or X2 and X2?, or X3 and X3? together represent ?O;
or X1 and X2 or X2 and X3 together represent —(CH2)2-6—, wherein individual hydrogen atoms can also be replaced by —F, —Cl, —Br, —I, —NO2, —CF3, —OR5, —CN or —C1-6-aliphatic;
or X1 and X1? or X2 and X2? or X3 and X3? in each case together represent a C3-6-cycloaliphatic, wherein individual hydrogen atoms can also be replaced by —F, —Cl, —Br, —I, —NO2, —CF3, —OR5, —CN or —C1-6-aliphatic;
R0 in each case independently represents —C1-8-aliphatic, —C3-12-cycloaliphatic, -aryl, -heteroaryl, —C1-8-aliphatic-C3-12-cycloaliphatic, —C1-8-aliphatic-aryl, —C1-8-aliphatic-heteroaryl, —C3-8-cycloaliphatic-C1-8-aliphatic, —C3-8-cycloaliphatic-aryl or —C3-8-cycloaliphatic-heteroaryl;
R1 and R2 independently of each other represent —H or —R0; or R1 and R2 together represent —CH2CH2OCH2CH2—, —CH2CH2NR8CH2CH2— or —(OH2)3-6—;
R3 represents —R0;
R4 represents —R11, —O(?O)R11, —O(?O)OR12, —C(?O)N(R12)2; —O(?O)—O—O(C?O)—R12—S(?O)R11 or —S(?O)2R11;
R5 in each case independently represents —H or —R0;
R6 and R7 independently of each other represent —H or —R0; or R6 and R7 together represent —CH2CH2OCH2CH2—, —CH2CH2NR10CH2CH2— or —(OH2)3-6—;
R8 represents —H, —R0 or —O(?O)R0;
R9 represents —H, —R0 or —OR5, or —NR6R7;
R10 represents —H or —C1-6-aliphatic;
R11 represents
a) —C1-6-alkyl, —C3-6-cycloalkyl, or —C1-3-alkyl-C3-6-cycloalkyl, wherein in the C3-6-cycloalkyl group a ring carbon atom can be replaced by an oxygen atom and —C1-6-alkyl, —C3-6-cycloalkyl or —C1-3-alkyl-C3-6-cycloalkyl is mono- or polysubstituted by substituents independently of each other selected from the group consisting of —NO2, —CHO, ?O, —O(?O)R0, —O(?O)H, —C(?O)—OH, —O(?O)OR0, —C(?O)NH2, —C(?O)NHR0, —C(?O)N(R0)2, —OH, —OR0, —OC(?O)H, —OC(?O)R0, —OC(?O)OR0, —OC(?O)NHR0, —OC(?O)N(R0)2, —SH, —SR0, —SO3H, —S(?O)1-2R0, —S(?O)1-2NH2, —S(?O)1-2—NHR0, —S(?O)1-2—N(R0)2, —NH2, —NHR0, —N(R0)2, —N+(R0)3, —N+(R0)2O?, —NHC(?O)R0, —NHC(?O)OR0, —NHC(?O)NH2, —NHC(?O)NHR0, —NH—C(?O)N(R0)2, —Si(R0)3 and —PO(OR0)2;
or
b) unsubstituted or mono- or polysubstituted —C7-8-alkyl, —C7-12-cycloalkyl or C3-12-cycloheteroalkyl having up to 3 hetero atoms in the ring selected from the group of O, N and S, with the proviso that heterocycles having only one oxygen atom as a hetero atom are excluded,
or
c) -aryl, -heteroaryl, —C4-8-cycloalkyl-C3-12-cycloaliphatic, —C1-8-aliphatic-aryl, —C1-8-aliphatic-heteroaryl, —C3-8-cycloaliphatic-C1-8-aliphatic, —C3-8-cycloaliphatic-aryl or —C3-8-cycloaliphatic-heteroaryl,
and R12 represents H, —C1-8-aliphatic, —C3-12-cycloaliphatic, -aryl, -heteroaryl, —C1-8-aliphatic-C3-12-cycloaliphatic, —C1-8-aliphatic-aryl, —C1-8-aliphatic-heteroaryl, —C3-8-cycloaliphatic-C1-8-aliphatic, —C3-8-cycloaliphatic-aryl or —C3-8-cycloaliphatic-heteroaryl;
wherein
“aliphatic” in each case is a branched or unbranched, saturated or a mono- or polyunsaturated, unsubstituted or mono- or polysubstituted, aliphatic hydrocarbon radical;
“cycloaliphatic” in each case is a saturated or mono- or polyunsaturated, unsubstituted or mono- or polysubstituted, alicyclic, mono- or multicyclic hydrocarbon radical;
wherein with respect to “aliphatic”, including —C4-8-alkyl, —C7-12-alkyl, and “cycloaliphatic” including —C7-12-cycloalkyl or C3-12-cycloheteroalkyl “mono- or polysubstituted” is understood as meaning substitution once or several times of one or more hydrogen atoms by —F, —Cl, —Br, —I, —CN, —NO2, —CHO, ?O, —R0, —O(?O)R0, —O(?O)H, —C(?O)—OH, —O(?O)OR0, —C(?O)NH2, —C(?O)NHR0, —C(?O)N(R0)2, —OH, —OR0, —OC(?O)H, —OC(?O)R0, —OC(?O)OR0, —OC(?O)NHR0, —OC(?O)N(R0)2, —SH, —SR0, —SO3H, —S(?O)1-2—R0, —S(?O)1-2NH2, —NH2, —NHR0, —N(R0)2, —N+(R0)3, —N+(R0)2O?, —NHC(?O)R0, —NHC(?O)OR0, —NHC(?O)NH2, —NHC(?O)NHR0, —NH—C(?O)N(R0)2, —Si(R0)3, —PO(OR0)2;
“aryl” in each case independently represents a carbocyclic ring system having at least one aromatic ring, but without hetero atoms in this ring, wherein the aryl radicals can optionally be fused with further saturated, (partially) unsaturated or aromatic ring systems and each aryl radical can be unsubstituted or mono- or polysubstituted, wherein the substituents on aryl can be identical or different and can be in any desired and possible position of the aryl;
“heteroaryl” represents a 5-, 6- or 7-membered cyclic aromatic radical which contains 1, 2, 3, 4 or 5 hetero atoms, wherein the hetero atoms are identical or different and are nitrogen, oxygen or sulfur and the heterocycle can be unsubstituted or mono- or polysubstituted; wherein in the case of substitution on the heterocycle the substituents can be identical or different and can be in any desired and possible position of the heteroaryl; and wherein the heterocycle can also be part of a bi- or polycyclic system;
wherein with respect to “aryl” and “heteroaryl”, “mono- or polysubstituted” is understood as meaning substitution once or several times of one or more hydrogen atoms of the ring system by substituents chosen from the group consisting of —F, —Cl, —Br, —I, —CN, —NO2, —CHO, ?O, —R0, —C(?O)R0, —C(?O)H, —C(?O)OH, —C(?O)OR0, —C(?O)NH2, —C(?O)NHR0, —C(?O)—N(R0)2, —OH, —O(CH2)1-2O—, —OR0, —OC(?O)H, —OC(?O)R0, —OC(?O)OR0, —OC(?O)NHR0, —OC(?O)N(R0)2, —SH, —SR0, —SO3H, —S(?O)1-2R0, —S(?O)1-2NH2, —NH2, —NHR0, —N(R0)2, —N+(R0)3, —N+(R0)2O?, —NHC(?O)R0, —NHC(?O)OR0, —NHC(?O)NH2, —NHC(?O)NHR0, —NHC(?O)N(R0)2, —Si(R0)3, —PO(OR0)2; wherein N ring atoms optionally present can in each case be oxidised (N-oxide);
in the form of an individual stereoisomer or mixture thereof, the free compounds and/or its physiologically acceptable salts and/or solvates.

US Pat. No. 10,214,519

PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS

Gilead Sciences, Inc., F...

1. A compound having the structure of formula (I):
wherein n is 1, 2, 3 or 4;
m is 1, 2, 3 or 4;
s is 1 or 2;
t is 1 or 2;
each R1 is independently selected from hydrogen, halo, cyano, hydroxy, amino, —C(O)Ra,—C(O)ORb, —C(O)NRaRb, —N(Ra)C(O)Rb, —S(O)NRaRb, —S(O)2NRaRb, —S(O)Ra, —S(O)2Ra, —NRaRb, —ORa, —SRb, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and 4-10 membered heterocyclyl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S;
wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 4-10 membered heterocyclyl is optionally substituted with one to four R100;
R2 is selected from hydrogen, halo, cyano, hydroxy, amino, —C(O)Ra, —C(O)ORb, —C(O)NRaRb, —N(Ra)C(O)Rb, —S(O)NRaRb, —S(O)2NRaRb, —S(O)Ra, —S(O)2Ra, —NRaRb, —ORa, —SRb, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and 4-10 membered heterocyclyl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S;
wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 4-10 membered heterocyclyl is optionally substituted with one to four R101;
R3 is selected from C6-10 aryl, 5-10 membered heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and 4-10 membered heterocyclyl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S;
wherein each C6-10 aryl, 5-10 membered heteroaryl and 4-10 membered heterocyclyl is optionally substituted with one to four R102;
R4 is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, acyl, C3-8 cycloalkyl and C1-6 alkyl sulfonyl;
each R5 is independently selected from hydrogen, halo, cyano, hydroxy, amino, —C(O)Ra, —C(O)ORb, —C(O)NRaRb, —N(Ra)C(O)Rb, —S(O)NRaRb, —S(O)2NRaRb, —S(O)Ra, —S(O)2Ra, —NRaRb, —ORa, —SRb, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and 4-10 membered heterocyclyl containing 1 to 4 heteroatoms selected from the group consisting of N, O, and S;
wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 4-10 membered heterocyclyl is optionally substituted with one to four R103;
each R6 is independently selected from hydrogen, halo, cyano, hydroxy, amino, —C(O)Ra, —C(O)ORb, —C(O)NRaRb, —N(Ra)C(O)Rb, —S(O)NRaRb, —S(O)2NRaRb, —S(O)Ra, —S(O)2Ra, —NRaRb, —ORa, —SRb, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl;
each Ra and Rb is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl;
wherein each C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, is optionally substituted with one to four R200;
each R100, R101, R102, and R103 is independently selected from hydrogen, halo, cyano, hydroxy, amino, oxo, thioxo, vinyl, —C(O)Ra, —C(O)ORb, —C(O)NRaRb, —N(Ra)C(O)Rb, —S(O)NRaRb, —S(O)2NRaRb, —S(O)Ra, —S(O)2Ra, —NRaRb, —ORa, —SRb, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 4-10 membered heterocyclyl;
wherein each C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, is optionally substituted with one to four R201; and,
each R200 and R201 is independently selected from hydrogen, halo, cyano, hydroxy, amino, oxo, thioxo, vinyl, —C(O)Rc, —C(O)ORd, —C(O)NRcRd, —N(Rc)C(O)Rd, —S(O)NRdRd, —S(O)2NRcRd, —S(O)Rc, —S(O)2Rc, —NRcRd, —ORc, —SRc, C1-6 alkyl, C2-6alkenyl and C2-6 alkynyl;
each Rc and Rd is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl;
or a pharmaceutically acceptable salt, isomer, or a mixture thereof.

US Pat. No. 10,214,517

LFA-1 INHIBITOR AND METHODS OF PREPARATION AND POLYMORPH THEREOF

SARCODE BIOSCIENCE INC., ...

1. A crystalline form of the compound of Formula I:
or a salt thereof,
which is crystalline Form II.

US Pat. No. 10,214,516

5-(N-FUSED TRICYCLIC ARYL TETRAHYDROISOQUINOLIN-6-YL) PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

VIIV HEALTHCARE UK (NO.5)...

1. A compound of Formula I
wherein:
R1 is selected from hydrogen, alkyl, or cycloalkyl;
R2 is tetrahydroisoquinolinyl substituted with 1 R6 substituent and is substituted with 0-3 halo or alkyl substituents;
R3 is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy;
R4 is selected from alkyl or haloalkyl;
R5 is alkyl; and
R6 is selected from phenanthrolinyl, phenanthridinyl, pyridofuropyrimidinyl, imidazothiazolopyridinyl, benzofuropyrimidinyl, benzothienopyrimidinyl, or pyrimidoindolyl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, thioalkyl, and haloalkoxy;
or a pharmaceutically acceptable salt thereof.

US Pat. No. 10,214,515

SUBSTITUTED PYRAZOLES AS INHIBITORS OF FIBROBLAST GROWTH FACTOR RECEPTOR

Zhejiang Hisun Pharmaceut...

20. A pharmaceutical composition comprising an effective amount of the compound according to claim 1, or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, and a pharmaceutically acceptable carrier or excipient, or a combination thereof.

US Pat. No. 10,214,514

HEDGEHOG ANTAGONISTS HAVING ZINC BINDING MOIETIES

Curis, Inc., Lexington, ...

1. A compound of Formula (VI):
or a pharmaceutically acceptable salt or prodrug thereof;
wherein
Q is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
G is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
K is halogen;
X is absent, —O—, —N(R2)—, —S—, —S(O)—, —S(O)2—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)N(R2)—, —N(R2)C(O)—, —S(O)2N(R2)—, or —N(R2)S(O)2—;
R2 is hydrogen or C1-C6-alkyl;
B is a direct bond, straight chain C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C1-C10 alkoxy, alkoxyC1-C10alkoxy, C1-C10 alkylamino, alkoxyC1-C10alkylamino, C1-C10 alkylcarbonylamino, C1-C10 alkylaminocarbonyl, aryloxyC1-C10alkoxy, aryloxyC1-C10alkylamino, aryloxyC1-C10alkylamino carbonyl, C1-C10-alkylaminoalkylaminocarbonyl, C1-C10 alkyl(N-alkyl)aminoalkyl-aminocarbonyl, alkylaminoalkylamino, alkylcarbonylaminoalkylamino, alkyl(N-alkyl)aminoalkylamino, (N-alkyl)alkylcarbonylaminoalkylamino, alkylaminoalkyl, alkylaminoalkylaminoalkyl, alkylpiperazinoalkyl, piperazinoalkyl, alkylpiperazino, alkenylaryloxyC1-C10alkoxy, alkenylarylaminoC1-C10alkoxy, alkenylaryllalkylaminoC1-C10alkoxy, alkenylaryloxyC1-C10alkylamino, alkenylaryloxyC1-C10alkylaminocarbonyl, piperazinoalkylaryl, heteroarylC1-C10alkyl, heteroarylC2-C10alkenyl, heteroarylC2-C10alkynyl, heteroarylC1-C10alkylamino, heteroarylC1-C10alkoxy, heteroaryloxyC1-C10alkyl, heteroaryloxyC2-C10alkenyl, heteroaryloxyC2-C10alkynyl, heteroaryloxyC1-C10alkylamino and heteroaryloxyC1-C10alkoxy, in each of which one or more methylenes is optionally interrupted or terminated by —O—, —N(R2)—, —C(O)—, —C(O)N(R2)—, or —C(O)O—; and
D is

where Y2 and R32 are absent, Z is N, W is O, R33 is H and R34 is hydroxyl.

US Pat. No. 10,214,513

HETEROCYCLIC COMPOUNDS USEFUL FOR KINASE INHIBITION

AMITECH THERAPEUTIC SOLUT...

1. A compound having the structure (IV) or an N-oxide, N,N?-dioxide, N,N?,N?-trioxide, or a pharmaceutically acceptable salt thereof:
wherein:
Z1 and Z2 are N;
Z3 is NR5, wherein R5 is hydrogen or an unsubstituted C1-C6 alkyl;
R1 is a C6 heteroaryl having 1 or 2 nitrogens optionally substituted with alkylthio or amino;
R4 is independently selected from a group consisting of hydrogen, halogen, and an unsubstituted C1-C6 alkyl;
n is 1 or 2; and
R13 is selected from a group consisting of the following structures:

US Pat. No. 10,214,512

FACTOR XIA INHIBITORS

1. A compound of the formula:
wherein
 is aryl or heteroaryl, which is optionally substituted with one to three groups independently selected from the group consisting of halo, oxo, cyano, R6, OR6, C(O)OR6, C1-3 alkyl-C(O)OR6, NR6R7, NH3+, C1-3 alkyl-NR7R8, NHC(O)R6, NHC(O)OR6, NHC(O)OC3-6 cycloalkyl, NHC(O)O—C1-3 alkyl-OR7, NHC(O)O—C1-3 alkyl-C(O)OH, C1-3 alkyl-NHC(O)OR7, NHC(O)NR7R8, NHSO2R6, C(O)NR7R8, CH2C(O)NR7R8 and NHCONH—C1-3 alkyl-heterocyclyl;
 is aryl or heteroaryl, which is optionally substituted with one to three groups independently selected from the group consisting of halo, cyano, oxido, oxo, cyclopropyl, R6, OR6, C(O)OR6, C1-3 alkyl- C(O)OR6, C(O)NR6R7 and NR6R7;
W is N or N+O?;
Y—X is —C(O)NR6—, —C(O)O—, —CHC(O)OR7—NR6—, —CR6R7—C(O)NR6—, —CHC(O)R7—NR6—, —CHC(O)OR7—CH2—, —CHC(O)NR6R7—NR6—, —CHCR6R7OR8—NR6—, —CHCR6R7—NR6R7—NR6—, —OC(O)NR6—, —NR6C(O)NR6- or -SO2NR6—;
Z is C3-8 alkylene or C3-8 alkenylene, wherein one or two of the carbon atoms in said alkylene and alkenylene may be replaced with O, NR6, C?O, C(O)NR6, NR6C(O), S, SO or SO2;
R1 is aryl, heteroaryl, C3-6 cycloalkyl or heteroalkyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups are optionally substituted with one to four substituents independently selected from the group consisting of halo, nitro, cyano, oxo, R6, OR6, C(O)R6, C(O)OR6, NR6R7, C1-3 alkyl-NR6R7, NHC(O)R7, NHC(O)OR7, C(NH)NR6R7, C3-6 cycloalkyl and heteroaryl (which is optionally substituted with halo, cyano, cyclopropyl, C(O)OH, C(O)NR6R7 or R6);
R2 is hydrogen, cyano, halo, R6 or OR6;
R3 is hydrogen, cyano, halo, R6 or OR6;
each R4 is independently C1-6 alkyl, CO2R6, COR6 or CONR7R8, wherein said alkyl is optionally substituted with one to three halo;
R5 is hydrogen, halo or C1-6 alkyl;
or one of R4 and R5 can be taken together with the atoms between them to form a 3 to 6 membered ring;
each R6 is independently hydrogen or C1-6 alkyl, which is optionally substituted with one to three groups independently selected from the group consisting of halo and hydroxy;
each R7 is independently hydrogen, C1-6 alkyl, heteroaryl or heterocyclyl, wherein said alkyl group is optionally substituted with one to three groups independently selected from the group consisting of halo and hydroxy;
each R8 is independently hydrogen or C1-6 alkyl;
Ra is hydrogen, hydroxy or O(C1-6 alkyl);
n is an integer between zero and three;
or a pharmaceutically acceptable salt thereof.

US Pat. No. 10,214,511

QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS

Bristol-Myers Squibb Comp...

1. A compound, wherein the compound isor salt thereof.

US Pat. No. 10,214,510

N-CYCLOALKYL-N-(BIHETEROCYCLYLETHYLENE)-(THIO)CARBOXAMIDE DERIVATIVES

Bayer CropScience Aktieng...

1. A compound of formula (I)
wherein:
A is selected from the group consisting of:
a heterocycle of formula (A?)

wherein:
R1, R2, and R3 are the same or different, and are independently a hydrogen atom; a halogen atom;
substituted or non-substituted C1-C5-alkyl C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C1-C5-alkoxy or C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A2)

wherein:
R4, R5, and R6 are the same or different, and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C1-C5-alkoxy or C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A3)

wherein:
R7 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl;
C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C1-C5-alkoxy or C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; and
R8 is a hydrogen atom or a substituted or non-substituted C1-C5-alkyl;
a heterocycle of formula (A4)

wherein:
R9, R10, and R11 are the same or different and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; amino; substituted or non-substituted C1-C5-alkoxy; substituted or non-substituted C1-C5-alkylsulfanyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; or C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A5)

wherein:
R12 and R13 are the same or different and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; substituted or non-substituted C1-C5-alkoxy; amino; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; or C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; and
R14 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; substituted or non-substituted C1-C5-alkoxy; amino; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; or C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A6)

wherein:
R15 is a hydrogen atom; a halogen atom; cyano; substituted or non-substituted C1-C5-alkyl; substituted or non-substituted C1-C5-alkoxy; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
R16 and R18 are the same or different and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkoxycarbonyl; substituted or non-substituted C1-C5-alkyl; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R17 is a hydrogen atom or substituted or non-substituted C1-C5-alkyl;
a heterocycle of formula (A7)

wherein:
R19 is a hydrogen atom or a C1-C5-alkyl; and
R20, R21, and R22 are the same or different, and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A8)

wherein:
R23 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R24 is a hydrogen atom or substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A9)

wherein:
R25 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R26 is a hydrogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A10)

wherein:
R27 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R28 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; amino; substituted or non-substituted C1-C5-alkylamino; or substituted or non-substituted di(C1-C5-alkyl)amino;
a heterocycle of formula (A11)

wherein:
R29 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; substituted or non-substituted C1-C5-alkoxy; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R30 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; amino; substituted or non-substituted C1-C5-alkylamino; or substituted or non-substituted di(C1-C5-alkyl)amino;
a heterocycle of formula (A12)

wherein:
R31 is a hydrogen atom or a substituted or non-substituted C1-C5-alkyl;
R32 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R33 is a hydrogen atom; a halogen atom; nitro; substituted or non-substituted C1-C5-alkyl; substituted or non-substituted C1-C5-alkoxy; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A13)

wherein:
R34 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; substituted or non-substituted C3-C5-cycloalkyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C1-C5-alkoxy; substituted or non-substituted C2-C5-alkynyloxy or C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different;
R35 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; cyano; substituted or non-substituted C1-C5-alkoxy; substituted or non-substituted C1-C5-alkylsulfanyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; amino; substituted or non-substituted C1-C5-alkylamino; or substituted or non-substituted di(C1-C5-alkyl)amino; and
R36 is a hydrogen atom or substituted or non-substituted C1-C5-alkyl;
a heterocycle of formula (A14)

wherein:
R37 and R38 are the same or different and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C1-C5-alkoxy; or a substituted or non-substituted C1-C5-alkylsulfanyl; and
R39 is a hydrogen atom or substituted or non-substituted C1-C5-alkyl;
a heterocycle of formula (A15)

wherein:
R40 and R41 are the same or different, and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A16)

wherein:
R42 and R43 are the same or different, and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; or amino;
a heterocycle of formula (A17)

wherein:
R44 and R45 are the same or different, and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A18)

wherein:
R47 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R46 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; or substituted or non-substituted C1-C5-alkylsulfanyl;
a heterocycle of formula (A19)

wherein:
R49 and R48 are the same or different, and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; substituted or non-substituted C1-C5-alkoxy; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A20)

wherein:
R50 and R51 are the same or different and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; substituted or non-substituted C1-C5-alkoxy; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A21)

wherein:
R52 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A22)

wherein:
R53 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different;
a heterocycle of formula (A23)

wherein:
R54 and R56 are the same or different, and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R55 is a hydrogen atom or substituted or non-substituted C1-C5-alkyl;
a heterocycle of formula (A24)

wherein:
R57 and R59 are the same or different, and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R58 is a hydrogen atom or substituted or non-substituted C1-C5-alkyl;
a heterocycle of formula (A25)

wherein:
R60 and R61 are the same or different and are independently a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl or C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; and
R62 is a hydrogen atom or substituted or non-substituted C1-C5-alkyl;
and
a heterocycle of formula (A26)

wherein:
R65 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; substituted or non-substituted C3-C5-cycloalkyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C1-C5-alkoxy; substituted or non-substituted C2-C5-alkynyloxy or C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different;
R63 is a hydrogen atom; a halogen atom; substituted or non-substituted C1-C5-alkyl; cyano; substituted or non-substituted C1-C5-alkoxy; substituted or non-substituted C1-C5-alkylsulfanyl; C1-C5-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; C1-C5-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different; amino; substituted or non-substituted C1-C5-alkylamino or di(C1-C5-alkyl)amino; and
R64 is a hydrogen atom or substituted or non-substituted C1-C5-alkyl;
T is O or S;
n is 0, 1, 2, 3, or 4;
L is a direct bond, CZ6Z7, O, S, SO, SO2, or NZ8;
B1 is a substituted or non-substituted thienyl ring; a substituted or non-substituted benzothiophenyl ring; a substituted or non-substituted pyridinyl ring; a substituted or non-substituted furyl ring; a substituted or non-substituted imidazo[1,2-a]pyridin-2-yl ring; or a substituted or non-substituted benzofuranyl ring;
B2 is a thienyl ring; a benzothiophenyl ring; a pyridinyl ring; a quinolinyl ring; a furyl ring; a benzofuranyl ring; or a pyrimidinyl ring; wherein B2 is optionally substituted by up to 6 Y groups which can be the same or different;
with the proviso that B2 is not a pyridyl ring when L is a direct bond, CZ6Z7, an oxygen atom, a sulfur atom, or NZ8, and A is a 1-C1-C4-alkyl-3-(difluoro or dichloro)methyl-5-(chloro or fluoro)-4-pyrazolyl moiety;
Z1 is a non-substituted C3-C7-cycloalkyl or a C3-C7-cycloalkyl substituted by up to 10 atoms or groups that are the same or different and that are selected from the group consisting of halogen atoms, cyano, C1-C8-alkyl, C1-C8-halogenoalkyl comprising up to 9 halogen atoms that are the same or different, C1-C8-alkoxy, C1-C8-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different, C1-C8-alkoxycarbonyl, C1-C8-halogenoalkoxycarbonyl comprising up to 9 halogen atoms that are the same or different, C1-C8-alkylaminocarbonyl, and di-C1-C8-alkylaminocarbonyl;
with the proviso that Z1 is not a non-substituted cyclopropyl when B1 is:
a 5-substituted (by B2) pyridin-2-yl group, or
a 6-substituted (by B2) pyridin-3-yl group, and
B2 is a thienyl or furyl group;
Z2, Z3, Z4 and Z5 are the same or different, and are independently a hydrogen atom; substituted or non-substituted C1-C8-alkyl; substituted or non-substituted C2-C8-alkenyl; substituted or non-substituted C2-C8-alkynyl; cyano; isonitrile; nitro; a halogen atom; substituted or non-substituted C1-C8-alkoxy; substituted or non-substituted C2-C8-alkenyloxy; substituted or non-substituted C2-C8-alkynyloxy; substituted or non-substituted C3-C7-cycloalkyl; substituted or non-substituted C1-C8-alkylsulfanyl; substituted or non-substituted C1-C8-alkylsulfonyl; substituted or non-substituted C1-C8-alkylsulfinyl; amino; substituted or non-substituted C1-C8-alkylamino; substituted or non-substituted di-C1-C8-alkylamino; substituted or non-substituted C1-C8-alkoxycarbonyl; substituted or non-substituted C1-C8-alkylcarbamoyl; substituted or non-substituted di-C1-C8-alkylcarbamoyl; or substituted or non-substituted N—C1-C8-alkyl-C1-C8-alkoxy-carbamoyl; or
Zi and Zi+1, wherein i is an integer from 2 to 4, are taken together with the carbon atom(s) to which they are attached to form a substituted or non-substituted C3-C7 cycloalkyl; or
Z5 and the substituent X vicinal to the point of attachment of the B1 heterocyclic ring are taken together with the consecutive carbon atoms to which they are attached to form a substituted or non-substituted 5-, 6-, or 7-membered, partly saturated, carbo- or heterocycle comprising up to 3 heteroatoms and Z4 is as defined above;
Z6 and Z7 are independently a hydrogen atom; a halogen atom; cyano; substituted or non-substituted C1-C8-alkyl; C1-C8-halogenoalkyl comprising 1 to 5 halogen atoms; substituted or non-substituted C1-C8-alkoxy; substituted or non-substituted C1-C8-alkylsulfanyl; or substituted or non-substituted C1-C8-alkoxycarbonyl; or
Z6 and Z7 are taken together with the carbon atom to which they are attached to form a C(?O) carbonyl group;
Z8 is a hydrogen atom; a substituted or non-substituted C1-C8-alkyl; a C1-C8-halogenoalkyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C2-C8-alkenyl; C2-C8-halogenoalkenyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C3-C8-alkynyl; C3-C8-halogenoalkynyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C3-C7-cycloalkyl; C3-C7-halogeno-cycloalkyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C3-C7-cycloalkyl-C1-C8-alkyl; formyl; substituted or non-substituted C1-C8-alkylcarbonyl; C1-C8-halogenoalkylcarbonyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C1-C8-alkoxycarbonyl; C1-C8-halogenoalkoxycarbonyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted C1-C8-alkylsulfonyl; C1-C8-halogenoalkylsulfonyl comprising up to 9 halogen atoms that are the same or different; substituted or non-substituted benzyl; or substituted or non-substituted phenylsulfonyl;
each X, where present, is independently a halogen atom; nitro; cyano; isonitrile; hydroxy; amino; sulfanyl; pentafluoro-?6-sulfanyl; formyl; formyloxy; formylamino; substituted or non-substituted (hydroxyimino)-C1-C8-alkyl; substituted or non-substituted (C1-C8-alkoxyimino)-C1-C8-alkyl; substituted or non-substituted (C2-C8-alkenyloxyimino)-C1-C8-alkyl; substituted or non-substituted (C2-C8-alkynyloxyimino)-C1-C8-alkyl; substituted or non-substituted (benzyloxyimino)-C1-C8-alkyl; carboxy; carbamoyl; N-hydroxycarbamoyl; carbamate; substituted or non-substituted C1-C8-alkyl; C1-C8-halogenoalkyl comprising 1 to 9 halogen atoms; substituted or non-substituted C2-C8-alkenyl; C2-C8-halogenoalkenyl comprising 1 to 9 halogen atoms; substituted or non-substituted C2-C8-alkynyl; C2-C8-halogenoalkynyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkoxy; C1-C8-halogenoalkoxy comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylsulfanyl; C1-C8-halogenoalkylsulfanyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylsulfinyl; C1-C8-halogenoalkylsulfinyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylsulfonyl; C1-C8-halogenoalkylsulfonyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylamino; substituted or non-substituted di-C1-C8-alkylamino; substituted or non-substituted C2-C8-alkenyloxy; C2-C8-halogenoalkenyloxy comprising 1 to 9 halogen atoms; substituted or non-substituted C3-C8-alkynyloxy; C2-C8-halogenoalkynyloxy comprising 1 to 9 halogen atoms; substituted or non-substituted C3-C7-cycloalkyl; C3-C7-halogenocycloalkyl comprising 1 to 9 halogen atoms; substituted or non-substituted (C3-C7-cycloalkyl)-C1-C8-alkyl; substituted or non-substituted C4-C7-cycloalkenyl; C4-C7-halogenocycloalkenyl comprising 1 to 9 halogen atoms; substituted or non-substituted (C3-C7-cycloalkyl)-C2-C8-alkenyl; substituted or non-substituted (C3-C7-cycloalkyl)-C2-C8-alkynyl; substituted or non-substituted tri(C1-C8)alkylsilyl; substituted or non-substituted tri(C1-C8)alkylsilyl-C1-C8-alkyl; substituted or non-substituted C1-C8-alkylcarbonyl; C1-C8-halogenoalkylcarbonyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylcarbonyloxy; C1-C8-halogenoalkylcarbonyloxy comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylcarbonylamino; C1-C8-halogenoalkylcarbonylamino comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkoxycarbonyl; C1-C8-halogenoalkoxycarbonyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkyloxycarbonyloxy; C1-C8-halogenoalkoxycarbonyloxy comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylcarbamoyl; substituted or non-substituted di-C1-C8-alkylcarbamoyl; substituted or non-substituted C1-C8-alkylaminocarbonyloxy; substituted or non-substituted di-C1-C8-alkylaminocarbonyloxy; substituted or non-substituted N—(C1-C8-alkyl)hydroxy carbamoyl; substituted or non-substituted C1-C8-alkoxycarbamoyl; substituted or non-substituted N—(C1-C8-alkyl)-C1-C8-alkoxycarbamoyl; aryl optionally substituted by up to 6 Q groups which are the same or different; aryl-C1-C8-alkyl optionally substituted by up to 6 Q groups which are the same or different; aryl-C2-C8-alkenyl optionally substituted by up to 6 Q groups which are the same or different; aryl-C2-C8-alkynyl optionally substituted by up to 6 Q groups which are the same or different; aryloxy optionally substituted by up to 6 Q groups which are the same or different; arylsulfanyl optionally substituted by up to 6 Q groups which are the same or different; arylamino optionally substituted by up to 6 Q groups which are the same or different; aryl-C1-C8-alkyloxy optionally substituted by up to 6 Q groups which are the same or different; aryl-C1-C8-alkylsulfanyl optionally substituted by up to 6 Q groups which are the same or different; or aryl-C1-C8-alkylamino optionally substituted by up to 6 Q groups which are the same or different;
each Y, where present, is independently a halogen atom; cyano; hydroxy; amino; sulfanyl; substituted or non-substituted C1-C8-alkyl; C1-C8-halogenoalkyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkoxy; C1-C8-halogenoalkoxy comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylsulfanyl; C1-C8-halogenoalkylsulfanyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylsulfinyl; C1-C8-halogenoalkylsulfinyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylsulfonyl; C1-C8-halogenoalkylsulfonyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkylamino; substituted or non-substituted di-C1-C8-alkylamino; substituted or non-substituted C1-C8-alkylcarbonyl; C1-C8-halogenoalkylcarbonyl comprising 1 to 9 halogen atoms; substituted or non-substituted C1-C8-alkoxycarbonyl; C1-C8-halogenoalkoxycarbonyl comprising 1 to 9 halogen atoms; or aryl optionally substituted by up to 6 Q groups which are the same or different;
each Q, where present, is independently a halogen atom, cyano, nitro, substituted or non-substituted C1-C8-alkyl, C1-C8-halogenoalkyl comprising up to 9 halogen atoms that are the same or different, substituted or non-substituted C1-C8-alkoxy, C1-C8-halogenoalkoxy comprising up to 9 halogen atoms that are the same or different, substituted or non-substituted C1-C8-alkylsulfanyl, C1-C8-halogenoalkylsulfanyl comprising up to 9 halogen atoms that are the same or different, substituted or non-substituted tri(C1-C8)alkylsilyl, substituted or non-substituted tri(C1-C8)alkylsilyl-C1-C8-alkyl, substituted or non-substituted (C1-C8-alkoxyimino)-C1-C8-alkyl, or substituted or non-substituted (benzyloxyimino)-C1-C8-alkyl;
or a salt, an N-oxide, a metal complex, a metalloid complex, an optically active isomer, or a geometric isomer thereof.

US Pat. No. 10,214,509

AMINO-SUBSTITUTED HETEROCYCLIC DERIVATIVES AS SODIUM CHANNEL INHIBITORS

Almirall, S.A., Barcelon...

1. A compound of Formula (I), or a pharmaceutically acceptable salt, N-oxide, or isotopically-labeled derivative thereof:
wherein:
G1 is —N— or —CH—;
G2 is —N— or —CR1, wherein R1 is chosen from a hydrogen atom and a linear or branched C1-4 alkyl group, with the proviso that at least one of G1 and G2 is —N—;
R2 is a is a hydrogen atom and R3 is a group of Formula (i):

wherein each G3 is independently —N— or —CR7, wherein R7 is chosen from a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a phenyl group, a linear or branched CIA alkyl group, a linear or branched (C1-4 alkoxy)-(C1-4 alkyl) group, —O—(CH2)1-2—NRaRb, —NRaRb, —CO—NRaRb, —ORc and —CH2—Rd;
R6 is chosen from a halogen atom, a cyano group, a linear or branched C1-4 alkyl group, a lineal linear or branched C1-4 haloalkyl group, a linear or branched C1-4 haloalkoxy group, —SO2—CF3 group, a O-phenyl group, a benzyl group and a —O-benzyl group;
or
R2 and R3 together with the nitrogen atom to which they are attached form the group of Formula (ii):

wherein each G4 is independently —CR8— or —N—, wherein R8 is chosen from a hydrogen atom and a halogen atom;
R4 is chosen from a halogen atom, a hydroxyl group, a linear or branched C1-4 alkyl group, a linear or branched C1-4 haloalkyl group, a linear or branched (C1-4 alkyl)-(C1-4 alkoxy) group, a linear or branched (C1-4 alkoxy)-(C1-4 alkyl) group, a linear or branched (C1-4 alkoxy)-(C1-4 alkoxy) group, —O(0-1)(CH2)(0-2)—NRaRb group, —O—(CH2)(0-2)Rc group, —O—(CHRf)1—CO—NRaRb group, —SO2—NRaRb group, a C6-6 aryl group, a monocyclic 5- to 8-membered heteroaryl group containing at least one heteroatom chosen from N, O and S, wherein the heteroaryl ring is optionally substituted with one or more substituents chosen from a halogen atom, a C1-2 alkyl group, a C1-2 alkoxy group and amino group optionally substituted with one or two C1-2 alkyl groups, and a 4- to 6-membered saturated or non-saturated heterocyclyl group containing at least one heteroatom chosen from N, O and S, wherein the heterocyclyl ring is optionally substituted with one or more substituents chosen from a C1-2 alkyl group, a C1-2 alkoxy group and —C(O)O—Re group, wherein Re represents a linear or branched C1-4 alkyl group, and wherein Rf is a hydrogen atom, a halogen atom or a linear or branched C1-4 alkyl group;
R5 is chosen from a hydrogen atom, a halogen atom, a linear or branched C1-4 alkyl group and a linear or branched C1-4 haloalkyl group;
Ra and Rb are independently chosen from a hydrogen atom, a linear or branched C1-4 alkyl group, a linear or branched (C1-4 alkoxy)-(C1-4 alkyl) group and a 5- to 8-membered monocyclic heteroaryl group containing at least one heteroatom chosen from N, S and O, or
Ra and Rb together with nitrogen atom to which they are attached form a 3- to 6-membered heterocyclyl group optionally containing a further heteroatom chosen from N, S and O, wherein the heterocyclyl group is optionally substituted with one or more substituents chosen from a C1-2 alkyl group;
Rc is chosen from a linear or branched C1-4 alkyl group, a linear or branched C1-4 hydroxyalkyl group, a linear or branched C1-4 haloalkyl group, a linear or branched (C1-4 alkoxy)-(C1-4 alkyl) group, a linear or branched (C1-4 alkyl)-(C1-4 alkoxy) group, a C6-8 aryl group, a monocyclic 5- to 8-membered heteroaryl group containing at least one heteroatom chosen from N, O and S, and a 4- to 6-membered heterocyclyl group containing at least one heteroatom chosen from N, O and S, wherein the heterocyclyl ring is optionally substituted with one or more substituents chosen from a C1-2 alkyl group and a C1-2 alkoxy group;
Rd is chosen from —NRaRb group, a 4- to 6-membered heterocyclyl group containing at least one heteroatom chosen from N, O and S, wherein the heterocyclyl group is optionally substituted with one or more substituents chosen from a halogen atom;
with the proviso that the compound is not chosen from:
5-amino-N-(4-ethylphenyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4-carboxamide,
5-amino-N-(2,4-dimethylphenyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4-carboxamide,
5-amino-1-(2,5-dimethylphenyl)-N-(4-fluorophenyl)-1H-1,2,3-triazole-4-carboxamide,
5-amino-N-(2,4-dichlorophenyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4-carboxamide,
5-amino-1-(2-methylphenyl)-N-(4-methylphenyl)-1H-1,2,3-triazole-4-carboxamide,
5-amino-N-(4-chlorophenyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4-carboxamide,
5-amino-N-(4-fluorophenyl)-1-(2-methylphenyl)-1H-1,2,3-triazole-4-carboxamide,
5-amino-N-(4-bromophenyl)-1-(2-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide,
5-amino-N-(2,4-difluorophenyl)-1-(2-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide,
5-amino-1-(2-methoxyphenyl)-N-(4-methylphenyl)-1H-1,2,3-triazole-4-carboxamide, and
5-amino-N-(4-fluorophenyl)-1-(2-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide.

US Pat. No. 10,214,508

NITROGEN-CONTAINING HETEROCYCLIC COMPOUND

Takeda Pharmaceutical Com...

1. A compound represented by the formula (I):
wherein
A is
a C3-10 cycloalkyl group
which is optionally further substituted by 1 to 3 substituents selected from
(1) a halogen atom,
(2) a C1-6 alkyl group optionally substituted by 1 to 3 hydroxy groups, and
(3) a C1-6 alkoxy group;
R1 is a hydrogen atom or a hydroxyl group;
R2 is a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group;
R3 is a hydrogen atom, a halogen atom, a cyano group, a C1-6 alkyl group optionally substituted by 1 to 3 halogen atoms, a C2-6 alkenyl group, a C3-6 cycloalkyl group, or a C1-6 alkoxy group optionally substituted by 1 to 3 halogen atoms;
R4 is a hydrogen atom or a halogen atom;
R5 is a pyrazolyl group optionally substituted by 1 to 3 C1-6 alkyl groups; and
X is CH,
or a salt thereof.

US Pat. No. 10,214,507

CARBAZOLE-CONTAINING AMIDES, CARBAMATES, AND UREAS AS CRYPTOCHROME MODULATORS

Reset Therapeutics, Inc.,...

1. A compound of formula I
or a pharmaceutically acceptable salt or hydrate thereof, wherein each of A, D, E, G, J, L, M, and Q is carbon;
each of R1 and R2 is independently selected from the group consisting of hydrogen, halo, cyano, nitro, —CF3, —CHF2, —CH2F, trifluoromethoxy, azido, hydroxyl, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C?O)—R8, —(C?O)—O—R8, —O—(C?O)—R8, —NR8(C?O)—R10, —(C?O)—NR8R9, —NR8R9, —NR8OR9, —S(O)cNR8R9, —S(O)d(C1-C6)alkyl, —O—SO2—R8, NR8—S(O)c, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(C6-C10)aryl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)f(C?O)(CR8R9)e(C6-C10)aryl, —(CR8R9)f(C?O)(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, and —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl;
each of R3 and R5 is independently selected from the group consisting of hydrogen, cyano, —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C?O)—R8, —(C?O)—O-R8, —(C?O)—NR8R9, —S(O)cNR8R9, —S(O)d(C1-C8)alkyl, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(C6-C10)aryl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)f(C?O)(CR8R9)e(C6-C10)aryl, —(CR8R9)f(C?O)(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, —(CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, and —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl;
wherein each of the R3 groups are optionally linked to each other as a 4-12 membered mono- or bicyclic ring;
wherein each of the R5 groups are optionally linked to each other as a 4-12 membered mono- or bicyclic ring;
R4 is selected from the group consisting of hydrogen, —CF3, —CHF2, —CH2F, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C?O)—R8, —(C?O)—O—R8, —(C?O)—NR8R9, —(CR8R9)d(3-10)-membered cycloalkyl, —(CR8R9)e(C6-C10)aryl, —(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)f(C?O)(CR8R9)e(C6-C10)aryl, —(CR8R9)f(C?O)(CR8R9)e(4-10)-membered heterocyclyl, —(CR8R9)eO(CR8R9)f(C6-C10)aryl, —(CR8R9)eO(CR8R9)f(4-10)-membered heterocyclyl, (CR8R9)fS(O)d(CR8R9)e(C6-C10)aryl, and —(CR8R9)fS(O)d(CR8R9)e(4-10)-membered heterocyclyl;
wherein R6 and R7 are linked to each other as a piperidinone ring, optionally substituted with one or more halo, (C1-C6)alkyl, (C3-C10)cycloalkyl, or (C6-C10)aryl;
each of R8, R9 and R10 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, —(CR11R12)e(3-10)-membered cycloalkyl, —(CR11R12)g(C6-C10)aryl, and —(CR11R12)g(4-10)-membered heterocyclyl;
any carbon atoms of the (C1-C6)alkyl, the (3-10)-membered cycloalkyl, the (C6-C10)aryl and the (4-10)-membered heterocyclyl of the foregoing R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R15, and R16 are independently optionally substituted with 1 to 3 R14 substituents each independently selected from the group consisting of halo, cyano, nitro, —CF3, —CHF2, —CH2F, trifluoromethoxy, azido, hydroxyl, —O—R15, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C?O)—R11, —(C?O)—R15, —(C?O)—O—R11, —(C?O)—O—R15, —O—(C?O)—R11, —O—(C?O)—R15, —NR11(C?O)—R13, —(C?O)—NR11R12, —(C?O)—NR11R15, —NR11R12, —NR11R15, —NR11OR12, —NR11OR15, —S(O)cNR11R12, —S(O)cNR11R15, —S(O)d(C1-C6)alkyl, —S(O)dR15, —O—SO2—R11, —O—SO2—R15, —NR11—S(O)c, —NR15—S(O)c, —(CR11R12)e(3-10)-membered cycloalkyl, —(CR11R12)e(C6-C10)aryl, —(CR11R12)e(4-10)-membered heterocyclyl, —(CR11R12)f(C?O)(CR11R12)e(C6-C10)aryl, —(CR11R12)f(C?O)(CR11R12)e(4-10)-membered heterocyclyl, —(CR11R12)eO(CR11R12)f(C6-C10)aryl, —(CR11R12)eO(CR11R12)f(4-10)-membered heterocyclyl, —(CR11R12)fS(O)d(CR11R12)e(C6-C10)aryl, and —(CR11R12)fS(O)d(CR11R12)e(4-10)-membered heterocyclyl;
any carbon atoms of the (C1-C6)alkyl, the (3-10)-membered cycloalkyl, the (C6-C10)aryl and the (4-10)-membered heterocyclyl of the foregoing R14 are independently optionally substituted with 1 to 3 R16 substituents each independently selected from the group consisting of halo, cyano, nitro, —CF3, —CHF2, —CH2F, trifluoromethoxy, azido, (CH2)eOH, (C1-C6)alkoxy, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C?O)—R11, —(C?O)—R15, —(C?O)—O—R11, —(C?O)—O—R15, —O—(C?O)—R11, —O—(C?O)—R15, —NR11(C?O)—R13, —(C?O)—NR11R12, —NR11R12, and —NR11R15; any nitrogen atoms of the (4-10)-membered heterocyclyl of the foregoing R1, R2, R3, R4, R8, R6, R7, R8, R9, R10, R14, and R15 are independently optionally substituted with (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, —(C?O)—R11, —(C?O)—O—R11, —(C?O)—NR11R12, —(CR11R12)e(3-10)-membered cycloalkyl, —(CR11R12)e(C6-C10)aryl, —(CR11R12)e(4-10)-membered heterocyclyl, —(CR11R12)f(C?O)(CR11R12)e(C6-C10)aryl, or —(CR11R12)f(C?O)(CR11R12)e(4-10)-membered heterocyclyl;
each R11, R12, and R13 are independently hydrogen or (C1-C6)alkyl;
R15 is —(CR11R12)e(3-10)-membered cycloalkyl, —(CR11R12)e(C6-C10)aryl, or —(CR11R12)e(4-10)-membered heterocyclyl;
a and b are each independently 1, 2, 3, or 4;
c is 1 or 2;
d is 0, 1, or 2; and
e, f, and g are each independently 0, 1, 2, 3, 4, or 5.

US Pat. No. 10,214,506

PREPARATION METHOD FOR 2-((4R,6S)-6-BROMOMETHYL-2-OXO-1,3-DIOXANE-4-YL)ACETATE

FUDAN UNIVERSITY, Shangh...

1. A preparation method for 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate, characterized in thata chemical formula of the 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate (I) is

wherein R is alkyl or cycloalkyl having 1 to 8 carbon atoms, or mono- or poly-substituted aryl or aralkyl, wherein 2((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate (I) is prepared by bromination and cyclization of 3-((substituted oxycarbonyl)oxy)-5-hexenoate as raw material with hypochlorite sad bromide in an organic solvent in presence of CO2, according to following reaction route:

wherein R and R? are same or different alkyl or cycloalkyl having 1 to 8 carbon atoms, or mono- or poly-substituted aryl or aralkyl;
M is alkali metal, alkaline earth metal or ammonium cation; wherein
the hypochlorite is selected from one or more of ethyl hypochlorite, isopropyl hypochlorite and tert-butyl hypochlorite;
the bromide is selected from one or more of potassium bromide, sodium bromide and ammonium bromide; and
the organic solvent is selected from one or more of ethyl acetate, dichloromethane, tetrahydrofuran, methanol, acetic acid, N,N-dimethyl formamide, acetone and acetonitrile.

US Pat. No. 10,214,505

KETAL ESTER COMPOUNDS AND USES THEREOF

GFBIOCHEMICALS LIMITED, ...

1. A compound having a structure corresponding to structure I:
wherein:
R1 is a linear, branched, or cyclic alkyl or aryl group comprising 6 to 12 carbon atoms and no oxygen atoms; and
R2 is a linear, branched, or cyclic alkyl or aryl group comprising 1 to 17 carbon atoms and no oxygen atoms.

US Pat. No. 10,214,503

2-(2,3-EPDXYPROPYL)PHENOL COMPOSITION AND METHOD OF MAKING

SABIC GLOBAL TECHNOLOGIES...

1. A composition comprising 1 to 40 weight percent 2-(2,3-epoxypropyl)-6-methylphenol, 30 to 90 weight percent 2-allyl-6-methylphenol, and 1 to 40 weight percent 8-methyl-3-chromanol, based on the total weight of the 2-(2,3-epoxypropyl)-6-methylphenol, 2-allyl-6-methylphenol, and 8-methyl-3-chromanol.

US Pat. No. 10,214,502

METHOD OF INHIBITING APOLIPOPROTEIN-E EXPRESSION WHILE INCREASING EXPRESSION OF AT LEAST ONE OF LDL-RECEPTOR PROTEIN OR ABCA1 PROTEIN COMPRISING ADMINISTERING A SMALL COMPOUND

Mayo Foundation for Medic...

1. A method for decreasing expression of apolipoprotein E and increasing expression of at least one of either LDL-receptor protein or AbcA1 protein comprising:selecting mammalian cells expressing apolipoprotein E and at least one of either LDL-receptor protein or AbcA1 protein;
contacting said mammalian cells with an effective amount of a compound having formula (I) in an amount sufficient to decrease expression of said apolipoprotein E and increase expression of at least one of said LDL-receptor protein or said AbcA1 protein in said mammalian cells:

 wherein Z may be at either position A or position B and may be selected from the group consisting of: CH2, CO, or SO2, and wherein R1 may be selected from the group consisting of:

US Pat. No. 10,214,501

3-ALKYL BICYCLIC [4,5,0] HYDROXAMIC ACIDS AS HDAC INHIBITORS

Forma Therapeutics, Inc.,...

1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
X1 is O;
X2 and X4 are each CR1R2;
X3 is CR1?R2?;
Y1and Y4 are not bonded to C(O)NHOH and are each CR1;
Y2 and Y3 are each CR1 when not bonded to C(O)NHOH and Y2 and Y3 are C when bonded to —C(O)NHOH;
L is selected from the group consisting of a bond, —(CR1R2)n—, —C(O)O—, —C(O)NR3—, —S(O)2—, —S(O)2NR3—, —S(O)—, and —S(O)NR3—, wherein L is bound to the ring nitrogen through the carbonyl or sulfonyl group;
R is independently selected from the group consisting of —H, —C1-C6 alkyl, —C2-C6 alkenyl, —C4-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, —C5-C12 spirocycle, heterocyclyl, spiroheterocyclyl, aryl, and heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, spirocycle, heterocyclyl, spiroheterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, oxo, —NO2, —CN, —R1, —R2, —OR3, —NHR3, —NR3R4, —S(O)2NR3R4, —S(O)2R1, —C(O)R1, —CO2R1, —NR3S(O)2R1, —S(O)R1, —S(O)NR3R4, —NR3S(O)R1, heterocycle, aryl, and heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O;
each R1 and R2 are independently, and at each occurrence, selected from the group consisting of —H, —R3, —R4, —C1-C6 alkyl, —C2-C6 alkenyl, —C4-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O, —OH, halogen, —NO2, —CN, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)2R5, —S(O)2(C1-C6 alkyl), —(C1-C6 alkyl)S(O)2R5, —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, —N(C1-C6 alkyl)S(O)2C1-C6 alkyl, and —(CHR5)—NR3R4, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, —NO2, oxo, —CN, —R5, —OR3, —NHR3, —NR3R4, —S(O)2N(R3)2, —S(O)2R5, —C(O)R5, —CO2R5, —NR3S(O)2R5, —S(O)R5, —S(O)NR3R4, —NR3S(O)R5, heterocycle, aryl, and heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O;
R1? and R2? are independently, and at each occurrence, selected from the group consisting of —H, —C1-C6 alkyl, —C2-C6 alkenyl, —C4-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, heterocyclyl, —OH, halogen, —NO2, —CN, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)2R5, —S(O)2(C1-C6 alkyl), —(C1-C6 alkyl)S(O)2R5, —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, —N(C1-C6 alkyl)S(O)2C1-C6 alkyl, and —(CHR5)—NR3R4, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, or heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, —NO2, oxo, —CN, —R5, —OR3, —NHR3, —NR3R4, —S(O)2N(R3)2, —S(O)2R5, —C(O)R5, —CO2R5, —NR3S(O)2R5, —S(O)R5, —S(O)NR3R4, —NR3S(O)R5, heterocycle, aryl, and heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O;
R3 and R4 are independently, at each occurrence, selected from the group consisting of —H, —C1-C6 alkyl, —C2-C6 alkenyl, —C4-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O, —S(O)2N(C1-C6 alkyl)2, —S(O)2(C1-C6 alkyl), —(C1-C6 alkyl)S(O)2R5, —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, and —(CHR5)—N(C1-C6 alkyl)2, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, —NO2, oxo, —CN, —R5, —O(C1-C6 alkyl), —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —S(O)2NH(C1-C6 alkyl), —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, —N(C1-C6 alkyl)S(O)2C1-C6 alkyl, —S(O)R5, —S(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)R5, heterocycle, aryl, and heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O;
or R3 and R can combine with the nitrogen atom to which they are attached to form a heterocycle, wherein each heterocycle is optionally substituted by —R1, —R2, —R4, —OR4, or —NR4R5;
R5 is independently, and at each occurrence, selected from the group consisting of —H, —C1-C6 alkyl, —C2-C6 alkenyl, —C4-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O, —OH, halogen, —NO2, —CN, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, —S(O)2NH(C1-C6 alkyl), —S(O)2N(C1-C6 alkyl)2, —S(O)2C1-C6 alkyl, —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, —N(C1-C6 alkyl)SO2C1-C6 alkyl, —S(O)(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), and —(CH2)nN(C1-C6 alkyl)2; and
n is independently, and at each occurrence, an integer from 0 to 6.

US Pat. No. 10,214,500

3-ALKYL-4-AMIDO-BICYCLIC [4,5,0] HYDROXAMIC ACIDS AS HDAC INHIBITORS

Forma Therapeutics, Inc.,...

1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
X1 is O;
X2 and X4 are each CR1R2;
X3 is CR1?R2?;
Y1 and Y4 are not bound to —C(O)NHOH and are each CR1;
Y2 and Y3 are each CR1 when not bonded to —C(O)NHOH and Y2 and Y3 are C when bonded to —C(O)NHOH;
L is selected from the group consisting of —C(O)—, —C(O)(CR1R2)m—, and —C(O)(CR1R2)mO—, wherein L is bound to the ring nitrogen through the carbonyl group;
R is independently selected from the group consisting of —H, —C1-C6 alkyl, —C2-C6 alkenyl, —C4-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, —C5-C12 spirocycle, heterocyclyl, spiroheterocyclyl, aryl, and heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, spirocycle, heterocyclyl, spiroheterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, oxo, —NO2, —CN, —R1, —R2, —OR3, —NHR3, —NR3R4, —S(O)2NR3R4, —S(O)2R1, —C(O)R1, —CO2R1, —NR3S(O)2R1, —S(O)R1, —S(O)NR3R4, —NR3S(O)R1, heterocycle, aryl, and heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O, with the proviso that R is not bound to L via a nitrogen atom;
R1 and R2 are independently, at each occurrence, selected from the group consisting of —H, —R3, —R4, —C1-C6 alkyl, —C2-C6 alkenyl, —C3-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O, —OH, halogen, —NO2, —CN, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)2R5, —S(O)2(C1-C6 alkyl), —(C1-C6 alkyl)S(O)2R5, —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, —N(C1-C6 alkyl)S(O)2C1-C6 alkyl, and —(CHR5)nNR3R4, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, —NO2, oxo, —CN, —R5, —OR3, —NHR3, —NR3R4, —S(O)2N(R3)2, —S(O)2R5, —C(O)R5, —CO2R5, —NR3S(O)2R5, —S(O)R5, —S(O)NR3R4, —NR3S(O)R5, heterocycle, aryl, and heteroaryl containing 1-5 heteroatoms selected from N, S, P, or O;
R1? and R2? are independently, at each occurrence, selected from the group consisting of —H, —C1-C6 alkyl, —C2-C6 alkenyl, —C3-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, heterocyclyl, —OH, halogen, —NO2, —CN, —NHC1-C6 alkyl, —N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)2R5, —S(O)2(C1-C6 alkyl), —(C1-C6 alkyl)S(O)2R5, —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, —N(C1-C6 alkyl)S(O)2C1-C6 alkyl, and —(CHR5)nNR3R4, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, or heterocyclyl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, —NO2, oxo, —CN, —R5, —OR3, —NHR3, —NR3R4, —S(O)2N(R3)2, —S(O)2R5, —C(O)R5, —CO2R5, —NR3S(O)2R5, —S(O)R5, —S(O)NR3R4, —NR3S(O)R5, heterocycle, aryl, and heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O;
R3 and R4 are independently, at each occurrence, selected from the group consisting of —H, —C1-C6 alkyl, —C2-C6 alkenyl, —C3-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, or O, —S(O)2N(C1-C6 alkyl)2, —S(O)2(C1-C6 alkyl), —(C1-C6 alkyl)S(O)2R5, —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, and —(CHR5)nN(C1-C6 alkyl)2, wherein each alkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more substituents selected from the group consisting of —OH, halogen, —NO2, oxo, —CN, —R5, —O(C1-C6 alkyl), —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(O)2N(C1-C6 alkyl)2, —S(O)2NHC1-C6 alkyl, —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, —N(C1-C6 alkyl)S(O)2C1-C6 alkyl, —S(O)R5, —S(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)R5, heterocycle, aryl, and heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O;
R5 is independently, at each occurrence, selected from the group consisting of —H, —C1-C6 alkyl, —C2-C6 alkenyl, —C3-C8 cycloalkenyl, —C2-C6 alkynyl, —C3-C8 cycloalkyl, heterocyclyl, aryl, heteroaryl containing 1-5 heteroatoms selected from the group consisting of N, S, P, and O, —OH, halogen, —NO2, —CN, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(O)2NH(C1-C6 alkyl), —S(O)2N(C1-C6 alkyl)2, —S(O)2C1-C6 alkyl, —C(O)C1-C6 alkyl, —CO2C1-C6 alkyl, —N(C1-C6 alkyl)SO2C1-C6 alkyl, —S(O)(C1-C6 alkyl), —S(O)N(C1-C6 alkyl)2, —N(C1-C6 alkyl)S(O)(C1-C6 alkyl), and —(CH2)nN(C1-C6 alkyl)2;
each n is independently and at each occurrence an integer from 0 to 6; and
each m is independently and at each occurrence an integer from 1 to 6.

US Pat. No. 10,214,498

HETEROCYCLIC COMPOUND

Takeda Pharmaceutical Com...

1. A compound represented by the formula (I):whereinring A is a pyrazole ring, a pyridine ring, or a pyrimidine ring;
X is CH2 or O; and
R is a hydrogen atom or a C1-6 alkyl group,
or a salt thereof.

US Pat. No. 10,214,497

PROCESS FOR THE PREPARATION OF A DUAL-ACTING ANGIOTENSIN RECEPTOR-NEPRILYSIN INHIBITOR COMPOUND

Hetero Labs, LTD, (IN)

1. A process for the preparation of amorphous form of Sacubitril/Valsartan sodium salt of Formula-II, which is stable at 30±5% RH:
which comprises,
i) reacting sacubitril of Formula-III,

with valsartan of Formula-IV

in a solvent, wherein solvent is selected from alcohol, ester, ketone and/or mixture thereof;
ii) adding sodium source to the above solution, wherein sodium source is selected from Sodium hydroxide, Sodium alkoxide and Sodium 2-ethylhexanoate;
iii) removing the solvent;
iv) adding an organic solvent, wherein organic solvent is selected from alcohol, ester, hydrocarbon solvent and/or mixture thereof;
v) removing the solvent;
vi) isolating the amorphous form of Sacubitril/Valsartan sodium salt of Formula-II, and
vii) optionally purifying the compound obtained in step vi).

US Pat. No. 10,214,492

HETEROCYCLIC INHIBITORS OF MCT4

Vettore, LLC, San Franci...

1. A compound of structural formula
and/or a salt thereof.

US Pat. No. 10,214,482

DIAMINE HAVING TERT-ALKYLAMINO GROUP AND PRIMARY AMINO GROUP FOR USE IN GAS SCRUBBING

BASF SE, Ludwigshafen (D...

1. An absorbent for removing carbon dioxide and/or hydrogen sulfide from fluid streams, comprising an aqueous solution of a compound of the general formula (I)
in which R1 and R3 are each independently selected from C1-4-alkyl and C1-4-hydroxyalkyl;
each R4 is independently selected from hydrogen, C1-4-alkyl and C1-4-hydroxyalkyl;each R5 is independently selected from hydrogen, C1-4-alkyl and C1-4-hydroxyalkyl;m is 2, 3, 4 or 5;
n is 2, 3, 4 or 5; and
o is an integer from 1 to 10.

US Pat. No. 10,214,481

TELOMERASE ACTIVATING COMPOUNDS AND METHODS OF USE THEREOF

BEN-GURION UNIVERSITY OF ...

1. A method of stimulating or increasing telomerase activity in a cell or tissue of a subject, said method comprising contacting said cell or tissue of said subject with an effective amount of a compound represented by the structure of Formula VI:
wherein
R1?, R3?, R4?, R6? R7?, and R9? are the same or different comprising halogen, aryl, C1-6alkyl, C1-6cycloalkyl, C1-6heterocycloalkyl, C1-6alkoxy, monoC1-6alkylamino, diC1-6alkylamino or arylamino; and
R10 is a C1-6alkyl.

US Pat. No. 10,214,480

SYNTHESIS PROCESS FOR CHIRAL CYCLOPROPYL ETHYNYL TERTIARY ALCOHOL COMPOUND

Shanghai Desano Pharmaceu...

1. A method for synthesizing a chiral cyclopropyl ethynyl tertiary alcohol compound, wherein the method comprises the following steps:(1) in an organic solvent, in the presence of an alkaline reagent and a salt thereof, reacting cyclopropyl acetylene with a chiral inducing agent, a chiral auxiliary reagent and zinc halide, thereby obtaining a first reaction mixture;
(2) reacting the first reaction mixture obtained in step (1) with 5-chloro-2-aminotrifluorobenzophenone to form a compound of formula I:

that is (S)-2-amino-5-chloro-?-cyclopropyl acetylene-?-trifluoromethylbenzyl alcohol;
wherein the salt is a sulfonate, a sulfinate, or a combination thereof;
and the alkaline agent is an alkali hydride.

US Pat. No. 10,214,479

SYNTHESIS OF AND COMPOSITIONS CONTAINING DIAMINOACETALS AND DIAMINOKETALS

Connora Technologies, Inc...

1. A process for preparing a compound represented by Formula (1) from a compound of Formula (2):
wherein:
each of R1 and R2 is independently selected from the group consisting of hydrogen, alkyl group, cycloalkyl group and aromatic group; or both of R1 and R2 forms a cyclic radical;
each of R3, R4, R5, and R6 is independently selected from the group consisting of hydrogen, alkyl group, cycloalkyl group and aromatic group;
R3 and R4 can combine with each other to form a cyclic radical;
R5 and R6 can combine with each other to form a cyclic radical; and
each m and n is independently an integer ranging from 1 to 3; the process comprising reducing the compound of Formula (2) with a reducing agent to produce the compound of Formula (1) at a temperature of from about 15° C. to about 200° C.

US Pat. No. 10,214,478

AMANTADINE NITRATE COMPOUNDS WITH NEURAL PROTECTIVE EFFECT, AND PREPARATION AND MEDICAL USE THEREOF

2. An amantadine nitrate compound with neural protective effects, having a structure of formula (III):or a pharmaceutically acceptable salt thereof,wherein:R2 is hydrogen, straight-chain or branched-chain or cyclic alkyl, optionally substituted-aryl or heteroaryl, or contains a nitrate ester group;
Z1 and Z2 are each independently a straight- or branched-carbon chain connecting to a nitrate ester group, wherein Z1 and Z2 each independently can be substituted with heteroatom, alkyl, aryl and heteroaryl, and Z1 and Z2 each independently have 1-6 carbon atoms;
wherein, the alkyl has up to 10 carbon atoms, the cyclic alkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; a substituent is N(CH3)2, F, Cl, Br, I, OCH3, CO2CH3, CN, aryl or heteroaryl; the aryl is monocyclic aryl, and the heteroaryl is monocyclic heteroaryl.

US Pat. No. 10,214,476

PAIN RELIEF COMPOUNDS

ECOLE NATIONALE SUPERIEUR...

1. A compound of formula (A1):
wherein:
R represents:

Q represents —CN;
X represents O, or —NH;
T represents:
a hydrogen atom;
a phenyl group;
a group

a cyclohexyl group;
Q2 represents O, or NH;
or a pharmaceutically acceptable salt of said compound.

US Pat. No. 10,214,475

MULTI-STEP SEPARATION PROCESS

BASF Pharma (Callanish) L...

1. A chromatographic separation process for recovering a polyunsaturated fatty acid (PUFA) product from a feed mixture, which comprises:(a) purifying the feed mixture in a first chromatographic separation step using as eluent a mixture of water and a first organic solvent, to obtain an intermediate product; and
(b) purifying the intermediate product in a second chromatographic separation step using as eluent a mixture of water and a second organic solvent, to obtain the PUFA product,
wherein the second organic solvent is different from the first organic solvent, and wherein the first chromatographic separation step comprises introducing the feed mixture into a simulated or actual moving bed chromatography apparatus and the second chromatographic separation step comprises introducing the intermediate product into a stationary bed chromatography apparatus.

US Pat. No. 10,214,474

OXIDATION OF URONIC ACIDS TO ALDARIC ACIDS

COOPERATIE KONINKLIJKE CO...

1. A process for the preparation of an aldaric acid by the oxidation of the corresponding uronic acid, wherein a starting material comprising the uronic acid is subjected to oxygen under the influence of a supported gold catalyst at a pH in a range of from 1-6, wherein the gold catalyst is a monometallic or bimetallic gold catalyst, wherein the oxidation of the corresponding uronic acid is carried out at a temperature in the range of from 30° C. to 100° C.

US Pat. No. 10,214,470

SYNTHESIS OF GUERBET ALCOHOLS

Arkema France, Colombes ...

1. A method for preparing a mixture of Guerbet alcohols, the method comprising:providing a starting material comprising a blend of at least two different primary alcohols, each of the at least two different primary alcohols independently being of the formula RCH2CH2OH, where R is hydrogen or a straight or branched chain alkyl group of 1 to 14 carbon atoms;
providing a base;
providing a catalyst;
mixing the starting material with the base and the catalyst in a reactor to form a reaction mixture;
heating the reaction mixture to a process temperature above the boiling point of water and under reaction conditions to cause condensation and dehydration of the at least two primary alcohols of the blend and to evolve vapor including water vapor;
removing the evolved vapor including water vapor from the reactor and feeding the removed vapor to a water separation unit, the water separation unit comprising a water outlet port;
removing part of the reaction mixture from the reactor, to form a removed part, and feeding the removed part to a liquid-liquid mixer-settler, the removed part comprising a mixture of Guerbet alcohols having respective boiling points, and alcohols having lower boiling points than the boiling points of the Guerbet alcohols;
feeding water from the water outlet port of the water separation unit, into the liquid-liquid mixer-settler to form a settler mixture;
separating an organic fraction from an aqueous fraction in the liquid-liquid mixer-settler;
feeding the organic fraction into an alcohols column;
forming dried alcohols from the organic fraction in the alcohols column;
separating the dried alcohols into a mixture of Guerbet alcohol products and the alcohols having lower boiling points than the boiling points of the Guerbet alcohols;
returning the alcohols having lower boiling points than the boiling points of the Guerbet alcohols, to the reaction mixture in the reactor; and
compensating for the removed part of the reaction mixture by adding appropriate amounts of new starting material comprising a blend of at least two different primary alcohols, base, and catalyst, to the reaction mixture in the reactor, for balancing the respective losses.

US Pat. No. 10,214,469

METHOD FOR PRODUCING HIGH-EFFICIENCY METHANOL CAPABLE OF REDUCING EMISSION OF CARBON DIOXIDE

KOREA RESEARCH INSTITUTE ...

1. A method for producing methanol, the method comprising:a first step of preparing mixed gas by using steam and natural gas supplied to a pre-reformer as raw materials and converting C2+ hydrocarbons contained in the natural gas into methane over a catalyst;
a second step of preparing a synthesis gas including carbon monoxide and hydrogen by reforming the mixed gas in a reformer filled with a reforming catalyst; and
a third step of a methanol synthesis process, in which methanol is prepared by using the synthesis gas as a raw material and reacting the synthesis gas in a methanol synthesis reactor filled with a methanol synthesis catalyst,
wherein
carbon dioxide is injected into the reformer of the second step, injected into the methanol synthesis reactor of the third step, or split to be injected into both of the reformer and the methanol synthesis reactor,
the methanol product and unreacted synthesis gas are separated, a portion of the separated unreacted synthesis gas is supplied to a heating furnace and combusted together with a natural gas, and
the mixed gas supplied to the reformer passes through at least one heat exchanger while post-combustion gas emitted from the heating furnace passes through the at least one heat exchanger to exchange heat between the post-combustion gas and the mixed gas by way of heat exchange.

US Pat. No. 10,214,467

SIMULATED MOVING BED XYLENES SEPARATION PROCESS, AND OPTIMIZED OPERATING CONDITIONS FOR UNITS TREATING PARAXYLENE-RICH FEEDS

IFP Energies nouvelles, ...


US Pat. No. 10,214,466

SYSTEMS AND METHODS FOR PRODUCING PROPYLENE

Saudi Arabian Oil Company...

1. A process for producing propylene, the process comprising:introducing a first stream comprising butene to a reactor, where the reactor comprises a metathesis catalyst and a cracking catalyst, the metathesis catalyst positioned generally upstream of the cracking catalyst;
at least partially metathesizing the first stream with the metathesis catalyst to form a metathesis-reaction product;
at least partially cracking the metathesis-reaction product with the cracking catalyst to form a cracking-reaction product comprising butene;
passing the cracking-reaction product out of the reactor in a cracking-reaction product stream; and
at least partially separating propylene from the cracking-reaction product stream to form a product stream comprising propylene,where:at least a portion of the butene in the cracking-reaction product stream is recycled by at least partially separating butene in the cracking-reaction product stream to form a recycle stream comprising butene; and
the first stream is a mixture of the recycle stream and a system inlet stream.

US Pat. No. 10,214,464

STEADY STATE HIGH TEMPERATURE REACTOR

UOP LLC, Des Plaines, IL...

1. A method to produce acetylene, comprising:introducing a fuel and oxygen into a fuel injection zone;
combusting said fuel and oxygen in a combustion zone to create a combustion gas stream;
cooling a sidewall of said combustion zone, wherein said cooling comprises flowing a coolant through at least one channel in said sidewall, wherein a portion of said coolant enters, via pores, said combustion zone through said sidewall;
accelerating the combustion gas stream and the portion of the coolant to supersonic speed in an expansion zone;
injecting feedstock into the combustion gas stream in a feedstock injection zone; and
reacting the feedstock to produce acetylene.

US Pat. No. 10,214,463

PRODUCTION METHOD AND PRODUCTION APPARATUS OF ?-OLEFIN OLIGOMER

MITSUBISHI CHEMICAL CORPO...

1. A method for producing an ?-olefin oligomer and reducing fouling in one or more downstream process equipment, comprising:oligomerizing an ?-olefin in a reaction solvent in the presence of a catalyst in a reactor to produce the ?-olefin oligomer comprising 1-hexene, wherein said reactor comprises a liquid phase and a gas phase;
introducing a portion of the gas phase into a heat exchanger;
cooling the portion of the gas phase in said heat exchanger to obtain a condensate liquid; and
dispersing the condensate liquid as droplets in the gas phase inside said reactor by an atomizer of a rotating disk spray system;
wherein said gas phase comprises a mist comprising a component of the catalyst and/or a portion of the ?-olefin, wherein the mist is generated by vaporization of the liquid phase, and wherein the mist is absorbed onto the condensate droplets thereby reducing fouling in the downstream process equipment caused by the mist.

US Pat. No. 10,214,461

PROCESS AND PLANT FOR PRODUCING OLEFINS FROM OXYGENATES

1. A process for producing olefins from oxygenates, the process comprising a first mode of operation for the production of propylene and a second mode of operation for the production of butylene,wherein the first mode of operation comprises the following steps:
(i) heterogeneously catalyzed converting of at least one oxygenate to a product stream containing C2 olefins, C3 olefins, C4 olefins, C5/6 hydrocarbon compounds, and C7+ hydrocarbon compounds, wherein the step of heterogeneously catalyzed converting is effected in two stages, wherein in the first stage methanol is converted with an equilibrium reaction into dimethyl ether and in the second stage dimethyl ether and unconverted methanol are converted to the product stream containing C2 olefins, C3 olefins, C4 olefins, C5/6 hydrocarbon compounds and C7+ hydrocarbon compounds, wherein the second stage of the heterogeneously catalyzed conversion is operated at an operating temperature of 390° C. to 500° C.,
(ii) recycling at least a portion of the C4 olefins into the second stage;
(iii) separating a stream comprising the C3 olefins from the product stream or a stream derived therefrom;
wherein the second mode of operation comprises the following steps:
(i) heterogeneously catalyzed converting of at least one oxygenate to a product stream containing C2 olefins, C3 olefins, C4 olefins, C5/6 hydrocarbon compounds, and C7+ hydrocarbon compounds, wherein the step of heterogeneously catalyzed converting is effected in two stages, wherein in the first stage methanol is converted with an equilibrium reaction into dimethyl ether and in the second stage dimethyl ether and unconverted methanol are converted to the product stream containing C2 olefins, C3 olefins, C4 olefins, C5/6 hydrocarbon compounds and C7+ hydrocarbon compounds, wherein the second stage of the heterogeneously catalyzed conversion is operated at an operating temperature of 390° C. to 500° C.,
(ii) recycling at least 10 wt-% of the C3 olefins into the second stage;
(iii) separating a stream comprising the C4 olefins from the product stream or a stream derived therefrom;
(iv) separating a stream comprising butane from the product stream or a stream derived therefrom;
(v) separating a stream comprising the C5/6 hydrocarbon compounds from the product stream or a stream derived therefrom;
(vi) separating a stream comprising the C7+ hydrocarbon compounds from the product stream or a stream derived therefrom;
(vii) recirculating of at least a portion of the C5/6 hydrocarbon stream and the C7+ hydrocarbon stream into the second stage in an amount effective to maintain the operating temperature of the second stage,
wherein the second mode of operation has a higher amount of C3 olefins recirculated to the second stage as compared to the first mode of operation,
wherein the second mode of operation is configured to provide an increased yield in the C4 olefins as compared to the first mode of operation.

US Pat. No. 10,214,460

BOOSTER COMPOSITION

Joyson Safety Systems Acq...

1. A composition comprising:a boron-containing compound selected from the group consisting of boron carbide, a metal boride, or a mixture thereof;
an oxidizer selected from the group consisting of at least one metal nitrate, metal nitrite, metal perchlorate, metal chlorate, metal oxide, and mixtures thereof; and
a secondary fuel, wherein said secondary fuel is selected from the group consisting of tetrazoles, triazoles, carboxylic acids, hydrazides, triazines, urea derivatives, guanidines, salts thereof or mixtures thereof; wherein the composition is free of ammonium nitrate and ammonium perchlorate.

US Pat. No. 10,214,459

CORROSION CONTROL METHODS FOR CORROSION-AGRESSIVE SOLUTIONS

CHEMTREAT, INC., Glen Al...

1. A method of preventing corrosion by a liquid solution of ammonium nitrate or urea ammonium nitrate, the method comprising:combining a stannous corrosion inhibitor composition with the liquid solution to provide a treated solution; and
contacting the treated solution with a metal surface of a container or conduit, wherein the treated solution has a pH of 6.0 or lower.

US Pat. No. 10,214,458

NUTRIENT RICH COMPOSITIONS

CALIFORNIA SAFE SOIL, LLC...

10. A nutrient rich emulsified hydrolysate soil amendment for administration by drip-line irrigation made from fresh food waste, comprising nutrients released by grinding, shredding, shearing, homogenization, filtering, diluting, enzymatic digestion by a combination of enzymes comprising at least one enzyme to digest proteins, at least one enzyme to digest fats and lipids, at least one enzyme to digest cellulosic material and at least one enzyme to digest other carbohydrates, and pasteurization; and a species selected from an acid stabilizer or an organic preservative, wherein the emulsified hydrolysate has a pH of between about 2.5 and below 3.5.

US Pat. No. 10,214,457

COMPOSITIONS CONTAINING GALLIUM AND/OR INDIUM AND METHODS OF FORMING THE SAME

General Electric Company,...

1. A composition, comprising: a silicon-containing material and about 0.001% to about 85% of an In-containing compound wherein the In-containing compound is selected from ZrO2, HfO2 or a combination thereof doped with about 0.1 to about 10 mole percent of In2O3.

US Pat. No. 10,214,456

SILICON COMPOSITIONS CONTAINING BORON AND METHODS OF FORMING THE SAME

General Electric Company,...

1. A composition, comprising: distinct, intertwined continuous phases including a first continuous phase comprising a silicon-containing material and a second continuous phase comprising a boron-doped refractory compound, and wherein the boron-doped refractory compound and the silicon-containing material have different compositions; andthe boron-doped refractory compound comprises a metal oxide doped with about 0.1% to about 10% by mole percent of B2O3, wherein the metal oxide comprises zirconium oxide, hafnium oxide, aluminum oxide, tantalum oxide, niobium oxide, gallium oxide, indium oxide, a rare earth oxide, a nickel oxide, or a mixture thereof, or;
the boron-doped refractory compound comprises a compound having the formula: Ln2-xBxO3 wherein Ln comprises Sc, Y, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, or a mixture thereof, and x is about 0.001 to about 1.

US Pat. No. 10,214,455

CERAMIC COMPOSITE MATERIALS AND METHODS

Florida State University ...

1. A method of forming a composite material, the method comprising:providing a carbon nanoscale fiber network which comprises a plurality of substantially aligned carbon nanoscale fibers;
infiltrating the carbon nanoscale fiber network with a first amount of a liquid ceramic precursor;
curing the first amount of the liquid ceramic precursor to form a cured ceramic precursor; and
pyrolyzing the cured ceramic precursor to form the composite material;
wherein the composite material comprises the carbon nanoscale fibers at a volume fraction of at least 35%.

US Pat. No. 10,214,454

STRUCTURE OF MICROPOWDER

INDUSTRIAL TECHNOLOGY RES...

1. Micropowder, comprising:a silicon carbide core; and
a carbon film covering the silicon carbide core,
wherein the silicon carbide core has a diameter of 50 micrometers to 500 micrometers, and the carbon film has a thickness of 20 nm to 200 nm,
wherein the micropowder is a hexagonal structure.

US Pat. No. 10,214,449

COATING COMPOSITIONS FOR ROOFING GRANULES, DARK COLORED ROOFING GRANULES WITH INCREASED SOLAR HEAT REFLECTANCE, SOLAR HEAT-REFLECTIVE SHINGLES AND PROCESS FOR PRODUCING THE SAME

CertainTeed Corporation, ...

1. A plurality of dark-colored roofing granules, each of the dark-colored roofing granules comprising:an inert base particle; and
a cured coating disposed about the inert base particle, the cured coating being a reaction product of a coating composition comprising:
an alkali metal silicate;
at least one non-clay latent heat reactant; and
at least one inorganic solar heat-reflective pigment, each of the at least one inorganic solar heat-reflective pigments having an L* less than 30 and a solar reflectance greater than 20 percent, and wherein the coating composition comprises at least about 5 percent to 25 percent of the at least one solar heat-reflective pigment,
wherein
the plurality of dark-colored roofing granules has an L* less than 30 and a solar reflectance greater than 20, and
wherein each of the dark-colored roofing granules lacks a light-colored base coat disposed between the inert base particle and the cured coating.

US Pat. No. 10,214,448

HIGH TEMPERATURE HYDRATOR

Carbon Engineering Ltd., ...

1. A method comprising:transferring at least one feed stream comprising calcium oxide, calcium carbonate, water, and a fluidizing gas into a fluidized bed;
contacting the calcium oxide with the water;
based on contacting the calcium oxide with the water, initiating a hydrating reaction;
producing, from the hydrating reaction, calcium hydroxide and heat;
transferring a portion of the heat of the hydrating reaction to the calcium carbonate; and
fluidizing the calcium oxide, calcium hydroxide, and the calcium carbonate into a first fluidization regime and a second fluidization regime, the first fluidization regime comprising at least a portion of the calcium carbonate and at least a portion of the calcium oxide, the second fluidization regime comprising at least a portion of the calcium hydroxide and at least another portion of the calcium oxide, the first fluidization regime different than the second fluidization regime.

US Pat. No. 10,214,447

COATED ARTICLE INCLUDING LOW-EMISSIVITY COATING, INSULATING GLASS UNIT INCLUDING COATED ARTICLE, AND/OR METHODS OF MAKING THE SAME

Guardian Glass, LLC, Aub...

1. A heat treated coated article including a low-E coating, comprising:a glass substrate, and the low-E coating of the heat treated coated article including the following layers moving from the glass substrate outwardly:
at least one first dielectric layer comprising silicon nitride;
a first layer comprising Ni and Ti on and contacting the first dielectric layer comprising silicon nitride;
an IR reflecting layer comprising Ag on and contacting the first layer comprising Ni and Ti;
a second layer that is metallic and comprising Ni and Ti on and contacting the IR reflecting layer comprising Ag, wherein each of the first and second layers comprising Ni and Ti comprise with respect to metal content from about 5 to 20% Ni and from about 80-95% Ti;
another dielectric layer comprising silicon nitride on the glass substrate over at least the second layer comprising Ni and Ti;
wherein the coating has a sheet resistance of less than or equal to about 1.2 ohms/sq.; and
wherein the coated article has a visible transmission of at least about 65%.

US Pat. No. 10,214,446

TEMPERABLE THREE LAYER ANTIREFLECTIVE COATING, COATED ARTICLE INCLUDING TEMPERABLE THREE LAYER ANTIREFLECTIVE COATING, AND/OR METHOD OF MAKING THE SAME

Guardian Glass, LLC, Aub...

1. A coated article comprising an antireflective coating supported by a first major surface of a substrate, wherein the antireflective coating comprises, in order moving away from the substrate:a silicon-inclusive medium index layer disposed, directly or indirectly, on the first major surface of the substrate;
a high index layer disposed over and contacting the medium index layer, the high index layer having a thickness of at least 85 nm;
a low index layer disposed over and contacting the high index layer;
wherein the medium index layer comprises silicon oxynitride and has an index of refraction of from about 1.65 to 2.0 at 380 nm, 550 nm, and 780 nm wavelengths, the high index layer has an index of refraction of at least about 2.0 at 380 nm, 550 nm, and 780 nm wavelengths, and the low index layer has an index of refraction of from about 1.4 to 1.6 at 380 nm, 550 nm, and 780 nm wavelengths.

US Pat. No. 10,214,445

ARTICLES WITH PATTERNED COATINGS

CORNING INCORPORATED, Co...

1. An article comprising:a substrate including a surface;
a patterned coating disposed on the surface forming a coated surface,
wherein, when a strain is applied to the article, the article exhibits a failure strain of 0.5% or greater,
wherein the patterned coating comprises a bimodal distribution of coating thickness, the bimodal distribution comprising a lower-mode thickness in the range from 10 nm to 90 nm, and a higher-mode thickness in the range from about 50 to about 5000 nm, and
wherein the substrate surface has a surface area and the patterned coating covers at least about 20% of the surface area.

US Pat. No. 10,214,444

METHOD FOR TREATING A SURFACE AND DEVICE IMPLEMENTED

1. A method for treating a surface of an object, said method consisting of:contacting the surface to be treated with a diffusion intermediate, said diffusion intermediate being impregnated with a corrosive solution prior to contacting or during said contacting, wherein said diffusion intermediate is a porous solid support that is chemically inert towards said corrosive solution; and
maintaining said surface to be treated in contact with said diffusion intermediate without any movement relative to each other,
wherein said treatment method removes or chemically erodes a layer of material from the surface of the object put into contact with the corrosive solution.

US Pat. No. 10,214,442

VITREOUS OR AT LEAST PARTLY CRYSTALLISED SEALING MATERIAL, JOINT CONNECTION, BARRIER LAYER, AND LAYER SYSTEM COMPRISING THE SEALING MATERIAL AND INTEGRATION THEREOF INTO COMPONENTS

SCHOTT AG, Mainz (DE)


wherein R2O3 is an oxide selected, individually or in any desired combination, from a group consisting of Ga2O3, In2O3, Dy2O3, Yb2O3, and any combinations thereof, and
wherein the composition is free from BaO and SrO apart from at most impurities.

US Pat. No. 10,214,441

CUTTING DEVICE

IHI CORPORATION, Tokyo (...

1. A cutting device comprising:a machining table which floats a workpiece having a plate shape;
a laser radiator positioned to radiate a laser beam onto the workpiece;
a coolant injector positioned to inject a coolant onto the workpiece; and
an actuator that relatively moves the workpiece with respect to the laser radiator and the coolant injector in a preset direction,
wherein the cutting device is configured to relatively move the workpiece in a direction preset by the actuator while radiating a laser beam from the laser radiator to a heating area set on the workpiece to heat the heating area, and to inject the coolant from the coolant injector to a cooling area set on the heated heating area to cool the cooling area, and
a plate member arranged to receive injection of the coolant from the coolant injector and scatter the coolant, wherein the plate member is installed at the machining table in front of the workpiece in a moving direction in which the workpiece relatively moves, and
wherein a baffle is positioned to provide a gap between the baffle and an upper surface of the workpiece, and wherein the baffle is positioned between a laser beam passage region and a coolant passage region, wherein the laser beam passage region is a region in which the laser beam radiated from the laser radiator passes between the laser radiator and the heating area, and wherein the coolant passage region is a region in which the coolant injected from the coolant injector passes between the coolant injector and the cooling area, and
a gas injector positioned to inject a gas from the laser beam passage region side toward the gap between the baffle and the workpiece.

US Pat. No. 10,214,440

METHOD FOR FORMING A HOT GLASS SHEET WITH TRANSVERSE CURVATURE

GLASSTECH, INC., Perrysb...

1. A method for forming a hot glass sheet having a pair of spaced end portions with distal extremities and also having an intermediate portion extending between its end portions, the method comprising:conveying the hot glass sheet on a conveyor into a heated chamber of a forming station to below an upper mold that is located above the conveyor and has a downwardly facing surface that has a downwardly convex shape with curvature in transverse directions;
moving the upper mold downwardly from an upper position to a lower position adjacent the glass sheet on the conveyor and operating a gas lift jet array to provide upwardly directed gas lift jets as the sole impetus for lifting the glass sheet from the conveyor and contacting the intermediate portion of the glass sheet with the downwardly facing surface of the upper mold for less than 50% of the distance between the distal extremities of the end portions of the glass sheet, and then moving the upper mold and the glass sheet upwardly to the upper position of the upper mold;
then moving a lower mold having a ring shape, that faces upwardly with a concave shape in transverse directions complementary to the downwardly convex shape of the downwardly facing surface of the upper mold, horizontally within the heated chamber to a location above the conveyor and below the upper mold in its upper position with the glass sheet supported on the upper mold and subsequently moving the upper mold downwardly and drawing a vacuum at the downwardly facing surface of the upper mold to press form the glass sheet between the upper and lower molds and provide curvature of the glass sheet in transverse directions, whereupon the upper mold is moved upwardly to its upper position with the press formed glass sheet supported on the upper mold by the vacuum drawn at its downwardly facing surface;
a pair of positioners being moved to blocking positions below the upper mold prior to operation of the gas lift jet array to limit upward movement of the end portions of the glass sheet toward the downwardly facing surface of the upper mold and thereby limit the extent of the intermediate portion of the glass sheet that initially contacts the downwardly facing surface of the upper mold, and the pair of positioners subsequently being moved from their blocking positions to unblocking positions to permit the subsequent press forming of the glass sheet between the upper and lower molds; and
then moving a delivery mold to below the press formed glass sheet on the upper mold in its upper position whereupon the vacuum drawn at the upper mold is terminated to release the glass sheet from the upper mold onto the delivery mold which is then moved out of the forming station for delivery of the press formed glass sheet.

US Pat. No. 10,214,439

NON-CONTACT VIBRATION SUPPRESSION DEVICE AND OBJECT PROCESSING METHOD

Corning Precision Materia...

1. A non-contact vibration suppressing device comprising:a cover;
first and second ultrasonic vibrators spaced apart from and facing each other such that an object is to be disposed therebetween, the first and second ultrasonic vibrators being disposed within the cover;
first and second ultrasonic generators disposed within the cover and connected to the first and second ultrasonic vibrators respectively to generate ultrasonic waves;
first and second vibration absorbers disposed within the cover and connected to the first and second ultrasonic vibrators respectively for absorbing vibrations of the first and second ultrasonic vibrators;
first and second frames disposed within the cover, the first and second frames connected to the first and second ultrasonic vibrators respectively to secure the first and second ultrasonic vibrators to the non-contact vibration suppressing device, and
first and second height adjustors disposed within the cover, the first and second height adjustors being connected to the first and second frames respectively to adjust a distance between the first and second ultrasonic vibrators;
wherein the first and second ultrasonic vibrators hold the object therebetween in a non-contact manner by generating ultrasonic vibrations and applying repelling force induced from the ultrasonic vibrations onto the object, thereby suppressing vibrations of the object.

US Pat. No. 10,214,438

CROSS CURRENT STAGED REVERSE OSMOSIS

BATTELLE MEMORIAL INSTITU...

1. A method for purifying a liquid feed stream to obtain a permeate performed under a system pressure, comprising:feeding the liquid feed stream to a system comprising:
(a) an initial reverse osmosis stage having: an initial high pressure side with an initial high pressure side inlet for receiving the liquid feed stream and an initial high pressure side outlet for outputting an initial recycle stream and an initial concentrate stream, and an initial low pressure side with an initial low pressure side inlet for receiving the initial recycle stream from the initial high pressure side outlet, and an initial low pressure side outlet for outputting a diluted stream, wherein the initial high pressure side outlet is split to form the initial recycle stream that is fed to the initial low pressure side inlet, and the initial concentrate stream;
(b) an intermediate section having one or more intermediate reverse osmosis stages arranged in series, wherein each intermediate stage has: an intermediate high pressure side with an intermediate high pressure side inlet and an intermediate high pressure side outlet, an intermediate low pressure side with an intermediate low pressure side inlet and an intermediate low pressure side outlet, an intermediate recycle stream and an intermediate concentrate stream exiting the intermediate high pressure side outlet, the intermediate recycle stream being sent to the intermediate low pressure side inlet, and an exit stream exiting the intermediate low pressure side outlet; and wherein the intermediate section receives the diluted stream from the initial reverse osmosis stage and outputs a purified stream, wherein the intermediate high pressure side outlet is split to form the intermediate recycle stream that is fed to the intermediate low pressure side inlet, and the intermediate concentrate stream; and
(c) a final reverse osmosis stage having: a final high pressure side having a final high pressure side inlet for receiving the purified stream and a final high pressure side outlet for outputting a reject stream, and a final low pressure side that outputs the permeate.

US Pat. No. 10,214,437

CROSS CURRENT STAGED REVERSE OSMOSIS

BATTELLE MEMORIAL INSTITU...

1. A system for purifying a liquid feed stream to obtain a permeate, comprising:(a) an initial reverse osmosis stage having: an initial high pressure side with an initial high pressure side inlet for receiving the liquid feed stream and an initial high pressure side outlet for outputting an initial recycle stream and an initial concentrate stream, and an initial low pressure side with an initial low pressure side inlet for receiving the initial recycle stream from the initial high pressure side outlet, and an initial low pressure side outlet for outputting a diluted stream, wherein the initial high pressure side outlet is split to form the initial recycle stream that is fed to the initial low pressure side inlet, and the initial concentrate stream;
(b) an intermediate section having one or more intermediate reverse osmosis stages arranged in series, wherein each intermediate stage has: an intermediate high pressure side with an intermediate high pressure side inlet and an intermediate high pressure side outlet, an intermediate low pressure side with an intermediate low pressure side inlet and an intermediate low pressure side outlet, an intermediate recycle stream and an intermediate concentrate stream exiting the intermediate high pressure side outlet, the intermediate recycle stream being sent to the intermediate low pressure side inlet, and an exit stream exiting the intermediate low pressure side outlet; and wherein the intermediate section receives the diluted stream from the initial reverse osmosis stage and outputs a purified stream, wherein the intermediate high pressure side outlet is split to form the intermediate recycle stream that is fed to the intermediate low pressure side inlet, and the intermediate concentrate stream; and
(c) a final reverse osmosis stage having: a final high pressure side having a final high pressure side inlet for receiving the purified stream and a final high pressure side outlet for outputting a reject stream, and a final low pressure side that outputs the permeate.

US Pat. No. 10,214,436

WASTEWATER TREATMENT DEVICE, BACTERIA BED USED FOR TREATING FOOD WASTE AND WASTEWATER, AND WASTEWATER TREATMENT METHOD USING BACTERIA BED

Hiroshi Ogawa, (JP) Keii...

16. A bacteria bed for decomposing food waste or, wastewater, comprising a carrier and microorganisms carried by the carrier, the carrier being formed of a surface part provided with a plurality of pores having the microorganisms carried therein and a core part formed of a synthetic resin, the surface part and the core part being different from each other in material and in specific gravity, the carrier having average specific gravities adjusted to match those of wastewater or a solid matter obtained by crushing food waste, the carrier carrying microorganisms and a prescribed amount of an enzyme activating activity of the microorganisms in the plurality of the pores.

US Pat. No. 10,214,433

BRINE TREATMENT SCALING CONTROL SYSTEM AND METHOD

Carollo Engineers, Inc., ...

1. A system for treating a brine stream, comprising:an electrodialysis-reversal system in communication with a concentrated brine stream source for receipt of a brine stream influent and production of a concentrated brine stream effluent and a lower salinity diluent stream effluent, wherein said electrodialysis-reversal system has a first process input connected to a demineralization portion of a membrane stack and a second process input connected to a concentrating portion of the membrane stack;
a brine treatment scaling control system in communication with said electrodialysis-reversal system for receipt of said concentrated brine stream effluent and production of a lowered salinity brine stream effluent, wherein said brine treatment scaling control system has a mixing vessel and a filter; and
a brine loop connected to said second process input of said electrodialysis-reversal system to return said lowered salinity brine stream effluent to said electrodialysis-reversal system.

US Pat. No. 10,214,432

METHOD AND DEVICE FOR ONLINE MONITORING OF WATER QUALITY

AQUA-Q AB, Farsta (SE)

1. A method for monitoring quality of water flowing in a pipe, the method comprising:diverting a flow of water from the pipe into a laser particle counter, the laser particle counter continuously counting particles within a particle size interval Sn in the diverted flow of water so as to continuously determine a number cin of particles within the particle size interval per volume of water;
comparing cin with a previously determined reference value crefn for determining the number of particles per volume of water flowing in the pipe;
taking a sample of the water from the pipe when cin exceeds a predetermined threshold value TVAn for more than a predetermined length of time tAn;
diverting a flow of water from the pipe into a filter that separates the flow into a permeate flow and a concentrate flow;
taking a sample of at least one of the permeate flow and the concentrate flow when cin exceeds a predetermined threshold value TVBn for more than a predetermined length of time tBn; and
sending an alarm signal when cin exceeds a predetermined threshold value TVCn for more than a predetermined length of time tCn.