Claims for Patent: 8,785,632

Summary for Patent: 8,785,632

Title:	Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
Abstract:	Enantiomerically pure compound of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.
Inventor(s):	Jingrong Jean Cui, Lee Andrew Funk, Lei Jia, Pei-Pei Kung, Jerry Jialun Meng, Mitchell David Nambu, Mason Alan Pairish, Hong Shen, Michelle Tran-Dube
Assignee:	Pfizer Corp SRL
Application Number:	US13/537,759
Patent Claims:	1. An enantiomerically pure compound of formula 1 wherein: Y is CR12; R1 is 5-12 membered heteroaryl; and each hydrogen in R1 is optionally replaced by one or more R3 groups; R2 is hydrogen; each R3 is independently halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C3-12 cycloalkyl, C6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —S(O)mR4, —SO2NR4R5, —S(O)2OR4, —NO2, —NR4R5, —(CR6R7)nOR4, —CN, —C(O)R4, —OC(O)R4, —O(CR6R7)nR4, —NR4C(O)R5, —(CR6R7)nC(O)OR4, —(CR6R7)nC(O)NR4R5, —(CR6R7)nNCR4R5, —C(═NR6)NR4R5, —NR4C(O)NR5R6, or —NR4S(O)pR5, each hydrogen in R3 is optionally replaced by R8, and R3 groups on adjacent atoms may combine to form a C6-12 aryl, 5-12 membered heteroaryl, C3-12 cycloalkyl or 3-12 membered heteroalicyclic group; each R4, R5, R6 and R7 is independently hydrogen, halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C3-12 cycloalkyl, C6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl; or any two of R4, R5, R6 and R7 bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from N, O, and S; or any two of R4, R5, R6 and R7 bound to the same carbon atom may be combined to form a C3-12 cycloalkyl, C6-12 aryl, 3-12 membered heteroalicyclic or 5-12 membered heteroaryl group; and each hydrogen in R4, R5, R6 and R7 is optionally replaced by R8; each R8 is independently halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C3-12 cycloalkyl, C6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —NH2, —CN, —OH, —O—C1-12 alkyl, —O—(CH2)nC3-12 cycloalkyl, —O—(CH2)nC6-12 aryl, —O—(CH2)n(3-12 membered heteroalicyclic) or —O—(CH2)n(5-12 membered heteroaryl); and each hydrogen in R8 is optionally replaced by R11; each R11 is independently halogen, C1-12 alkyl, C3-12 cycloalkyl, C6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —O—C1-12 alkyl, —O—(CH2)nC3-12 cycloalkyl, —O—(CH2)nC6-12 aryl, —O—(CH2)n(3-12 membered heteroalicyclic), —O—(CH2)n(5-12 membered heteroaryl) or —CN, and each hydrogen in R11 is optionally substituted by halogen, —OH, —CN, —C1-12 alkyl which may be partially or fully halogenated, or —O—C1-12 alkyl which may be partially or fully halogenated; R12 is hydrogen; each m is independently 0, 1 or 2; each n is independently 0, 1, 2, 3 or 4; and each p is independently 1 or 2; or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein R1 is a furan, thiophene, pyrrole, thiazole, imidazole pyrazole, isoxazole, isothiazole, oxadiazole, triazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, or triazine, and each hydrogen in R1 is optionally replaced by R3. 3. An enantiomerically pure compound of formula 1a wherein: Y is CH; R1 is pyrazole; and each hydrogen in R1 is optionally replaced by R3; each R3 is independently 3-12 membered heteroalicyclic, and each hydrogen in R3 is optionally replaced by R8; each R8 is independently halogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C3-12 cycloalkyl, C6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —NH2, —CN, —OH, —O—C1-12 alkyl, —O—(CH2)nC3-12 cycloalkyl, —O—(CH2)nC6-12 aryl, —O—(CH2)n(3-12 membered heteroalicyclic) or —O—(CH2)n(5-12 membered heteroaryl); and each hydrogen in R8 is optionally replaced by R11; each R11 is independently halogen, C1-12 alkyl, C3-12 cycloalkyl, C6-12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, —O—C1-12 alkyl, —O—(CH2)nC3-12 cycloalkyl, —O—(CH2)nC6-12 aryl, —O—(CH2)n(3-12 membered heteroalicyclic), —O—(CH2)n(5-12 membered heteroaryl) or —CN, and each hydrogen in R11 is optionally substituted by halogen, —OH, —CN, —C1-12 alkyl which may be partially or fully halogenated, or —O—C1-12 alkyl which may be partially or fully halogenated; and each n is independently 0, 1, 2, 3 or 4; or a pharmaceutically acceptable salt thereof. 4. An enantiomerically pure compound selected from the group consisting of 3[(R)-1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-[1-(1-methyl-piperidin-4-yl)-1H-pyrazol-4-yl]-pyridin-2-ylamine; 1-[4-(4-{6-Amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl]-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidin-1-yl]-2-hydroxy-ethanone; and 3-[(R)-1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine; or a pharmaceutically acceptable salt thereof.