US Patent No. 10,428,083

HETEROCYCLYLMETHYL-THIENOURACILE AS ANTAGONISTS OF THE ADENOSINE-A2B-RECEPTOR


Patent No. 10,428,083
Issue Date October 01, 2019
Title Heterocyclylmethyl-thienouracile As Antagonists Of The Adenosine-a2b-receptor
Inventorship Dirk Kosemund, Berlin (DE)
Martina Delbeck, Heiligenhaus (DE)
Bernd Kalthof, Wuppertal (DE)
Klemens Lustig, Wuppertal (DE)
Assignee BAYER PHARMA AKTIENGESELLSCHAFT, Berlin (DE)

Claim of US Patent No. 10,428,083

1. Compound of the formula (I)
in which
the ring A is an azaheterocycle of the formula

in which * marks the bond to the adjoining CH(R1) group,
R5 is hydrogen, (C1-C4)-alkyl, hydroxyl, (C1-C4)-alkoxy, amino, (C1-C5)-alkanoylamino or (C1-C4)-alkoxycarbonylamino,
R6 is hydrogen, methyl or ethyl,
R7A and R7B are the same or different and are independently hydrogen or (C1-C4)-alkyl,
R8 is hydrogen, (C1-C4)-alkyl, (C2-C4)-alkenyl, (C1-C5)-alkanoyl or (C1-C4)-alkoxycarbonyl,
where (C1-C4)-alkyl may be up to disubstituted by hydroxyl,
R9A and R9B are the same or different and are independently hydrogen or (C1-C4)-alkyl
and
X is O, N(R10) or S, in which
R10 is hydrogen, cyano or (C1-C4)-alkoxycarbonyl,
R1 is hydrogen or methyl,
R2 is hydrogen, methyl or ethyl, where methyl and ethyl may be up to trisubstituted by fluorine,
R3 is (C2-C6)-alkyl, (C2-C6)-alkenyl or (C2-C6)-alkynyl,
where (C2-C6)-alkyl may be substituted by a radical selected from the group of hydroxyl, methoxy, ethoxy, trifluoromethoxy, cyclopropyl, cyclobutyl, oxetanyl and phenyl, and up to trisubstituted by fluorine,
and
(C2-C6)-alkenyl may be up to trisubstituted by fluorine,
where the cyclopropyl and cyclobutyl groups mentioned may in turn be up to disubstituted, identically or differently, by a radical selected from fluorine and methyl,
or
R3 is a group of the formula —CH2—R14 in which
R14 is cyclopropyl, cyclobutyl, oxetanyl or tetrahydrofuranyl, where cyclopropyl, cyclobutyl and oxetanyl may be up to disubstituted, identically or differently, by a radical selected from fluorine and methyl,
and
R4 is (C1-C6)-alkyl or (C2-C6)-alkenyl,
where (C1-C6)-alkyl may be up to pentasubstituted and (C2-C6)-alkenyl up to trisubstituted by fluorine
and
where one CH2 group in (C1-C6)-alkyl may be exchanged for —O—, —S— or —S(O)2—, with the proviso that there are at least two carbon atoms between such a heteroatom and the uracil N1 atom,
or
R4 is a group of the formula —(CH2)m—CN, —(CH2)n—R11 or —(CH2)p—R12, in which
m is the number 1, 2, 3 or 4,
n is the number 2 or 3,
p is the number 1 or 2,
R11 is dimethylamino, diethylamino or azetidino
and
R12 is (C3-C6)-cycloalkyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl or 5-membered azaheteroaryl,
where (C3-C6)-cycloalkyl may be up to disubstituted, identically or differently, by a radical selected from fluorine and methyl
and
azaheteroaryl may be up to disubstituted, identically or differently, by a radical selected from methyl and trifluoromethyl,
or
R4 is a group of the formula —(CH2)2—O—R13 in which
R13 is (C3-C6)-cycloalkyl,
and a salt, a solvate, and a solvate of the salt thereof.