c-MET modulators and method of use
View Patent ↗A compound for modulating kinase activity according to Formula I, or a pharmaceutically acceptable salt thereof, Wherein J 1 , J 2 , J 3 , R 2 , J 4 , Z, Ar and R 3 are as defined in the specification, compositions thereof, and methods of use thereof.
1. A compound of formula IVc:
wherein:
J 1 is ═CH—;
J 2 is ═C(R 1 )—;
J 3 is ═N—;
J 4 is ═N—;
J 5 is C—H or C—F;
Z is O;
R 1 is independently selected from halogen, trihalomethyl, —CN, —NO 2 , —OR 20 , —N(R 20 )R 20 , —S(O) 0-2 R 20 , —SO 2 N(R 20 )R 20 , —CO 2 R 20 , —C(O)N(R 20 )R 20 , —N(R 20 )SO 2 R 20 , —N(R 20 )C(O)R 20 , —NHCO 2 R 20 , —C(O)R 20 , optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl;
R 2 is H;
each R 3a is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —OR 20 , —N(R 20 )R 20 , —S(O) 0-2 R 20 , —SO 2 N(R 20 )R 20 , —CO 2 R 20 , —C(O)N(R 20 )R 20 , —N(R 20 )SO 2 R 20 , —N(R 20 )C(O)R 20 , —NHCO 2 R 20 , —C(O)R 20 , optionally substituted C 1-6 alkyl, and optionally substituted heterocyclyl;
each R 20 is independently —H, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl; or two of R 20 , when taken together with a common nitrogen to which they are attached, can form an optionally substituted five- to seven-membered heterocyclyl, said optionally substituted five- to seven-membered heterocyclyl optionally containing at least one additional annular heteroatom selected from N, O, S, and P; and
each R 70 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —OR 20 , —N(R 20 )R 20 , —S(O) 0-2 R 20 , —SO 2 N(R 20 )R 20 , —CO 2 R 20 , —C(O)N(R 20 )R 20 , —N(R 20 )SO 2 R 20 , —N(R 20 )C(O)R 20 , —NHCO 2 R 20 , —C(O)R 20 , optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl C 1-6 alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclyl C 1-6 alkyl.
2. A compound selected from:
Entry
Name
Structure
2
N-(4-fluorophenyl)-N′-[3-fluoro-4-(7H- pyrrolo[2,3-d]pyrimidin-4- yloxy)phenyl]cyclopropane-1,1- dicarboxamide
12
N-{3-fluoro-4-[(6-{[(2-morpholin-4- ylethyl)amino]carbonyl}-7H-pyrrolo[2,3- d]pyrimidin-4-yl)oxy]phenyl}-N′-(4- fluorophenyl)cyclopropane-1,1- dicarboxamide
3. A pharmaceutical composition comprising a compound according to claim 1 or 2 and a pharmaceutically acceptable carrier.