US Patent No. 9,133,215

MACROCYCLIC DERIVATIVES FOR THE TREATMENT OF DISEASES


Patent No. 9,133,215
Issue Date September 15, 2015
Title Macrocyclic Derivatives For The Treatment Of Diseases
Inventorship Simon Bailey, San Diego, CA (US)
Benjamin Joseph Burke, San Diego, CA (US)
Michael Raymond Collins, San Diego, CA (US)
Jingrong Jean Cui, San Diego, CA (US)
Judith Gail Deal, Wildomar, CA (US)
Robert Louis Hoffman, San Marcos, CA (US)
Qinhua Huang, San Diego, CA (US)
Ted William Johnson, Carlsbad, CA (US)
Robert Steven Kania, San Diego, CA (US)
John Charles Kath, La Mesa, CA (US)
Phuong Thi Quy Le, San Diego, CA (US)
Michele Ann McTigue, Encinitas, CA (US)
Cynthia Louise Palmer, La Mesa, CA (US)
Paul Francis Richardson, San Diego, CA (US)
Neal William Sach, San Diego, CA (US)
Assignee Pfizer Inc., New York, NY (US)

Claim of US Patent No. 9,133,215

1. A compound of formula (VI)
wherein:
A is a ring selected from C6-C12 aryl and 5-6 membered heteroaryl;

R1 is selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl, wherein each hydrogen on said C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, —OH,
—NH2, —S(O)tR9, —S(O)2NR9R10 , —S(O)2OR9, —NO2, —CN, —OR9, —C(O)R9, —OC(O)R9, —NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R10, —NR9 C(O)NR9R10, —NR or —C(O)NR9R10;

each R2 is independently selected from the group consisting of halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, —S(O)tR7, —S(O)2NR7R8, —S(O)2OR7, —NO2, —(CR5R6)qNR7R8, —N(CR5R6)(CR5R6)qNH7R8, —OR7, —O(CR5R6)(CR5R6)qOR7, —O(CR5R6)(CR5R6)qR7, —CN, —C(O)R7, —OC(O)R7, —O(CR5R6)qR7, —NR7C(O)R8, —(CR5R6)qC(O)OR7, —(CR5R6)qNR7R8, —C(?NR7)NR7R8, —NR7C(O)NR7R8, —NR7S(O)2R8 and —(CR5R6)qC(O)NR7R8; wherein each hydrogen on said C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, —OH,
—NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —OR9, —CN, —C(O)R9,—OC(O)R9, —NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R10, —NR9C(O)NR9R10—NR9S(O)2R10or —C(O)NR9R10;

R3 and R4 are each independently selected from hydrogen, C1-C6 alkyl and C3-C6 cycloalkyl, wherein each hydrogen on C1-C6 alkyl and C3-C6 cycloalkyl may be independently optionally substituted by halogen, —OH, —NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —CN, —OR9, —C(O)R9,—OC(O)R9, —NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R10, —NR9C(O)NR9R10, —NR9S(O)2R10or —C(O)NR9R10;

each R5 and R6 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, —OH, —NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —CN, —OR9, —C(O)R9,—OC(O)R9, —NR9C(O)R1° , —C(O)OR9, —C(?NR9)NR9R10, —NR9C(O)NR9R10, —NR9S(O)2R10and —C(O)NR9R10; wherein each hydrogen on said C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, —OH,
—NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —CN, —OR9, —C(O)R9, —OC(O)R9,—NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R1° , —NR —NR or —C(O)NR9R10;

each R7 and R8 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl, wherein each hydrogen on said C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, —OH,
—NH2, —S(O)tR9, —S(O)2NR9R10, —S(O)2OR9, —NO2, —OR9, —CN, —C(O)R9, —OC(O)R9, —NR9C(O)R10, —C(O)OR9, —C(?NR9)NR9R10, —NR9S(O)2R10or —C(O)NR9R10;

each R9 and R10is independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C6-C12 aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl;

p is 0, 1, 2, 3 or 4;
each q is independently 0, 1, 2 or 3; and
each t is independently 0, 1 or 2;
or a pharmaceutically acceptable salt thereof.