Claims for Patent: 8,039,479

Summary for Patent: 8,039,479

Title:	Compounds and compositions as protein kinase inhibitors
Abstract:	The invention provides novel pyrimidine and pyridine derivatives and pharmaceutical compositions thereof, and methods for using such compounds. For example, the pyrimidine and pyridine derivatives of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of anaplastic lymphoma kinase (ALK) activity, focal adhesion kinase (FAK), zeta-chain-associated protein kinase 70 (ZAP-70), insulin-like growth factor (IGF-1R), or a combination thereof.
Inventor(s):	Pierre-Yves Michellys, Wei Pei, Thomas H. Marsilje, Bei Chen, Tetsuo Uno
Assignee:	Novartis AG
Application Number:	US11/943,436
Patent Claims:	1. A compound having Formula (2): or pharmaceutically acceptable salts thereof; wherein R1 is halo or C1-6 alkyl; R2 is H; R3 is (CR2)0-2SO2R12; R4 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; OR12, NR(R12), halo, nitro, SO2R12, (CR2)pR13 or X; or R4 is H; R6 is isopropoxy or methoxy; one of R8 and R9 is (CR2)qY and the other is C1-6 alkyl, cyano, C(O)O0-1R12, CONR(R12) or CONR(CR2)pNR(R12); X is (CR2)qY, cyano, C(O)O0-1R12, CONR(R12), CONR(CR2)pNR(R12), CONR(CR2)pOR12, CONR(CR2)pSR12, CONR(CR2)pS(O)1-2R12 or (CR2)1-6NR(CR2)pOR12; Y is pyrrolidinyl, piperidinyl or azetidinyl, each of which is attached to the phenyl ring via a carbon atom; R12 and R13 are independently 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 5-7 membered heterocyclic ring comprising N, O and/or S; aryl or heteroaryl; or R12 is H or C1-6 alkyl; R is H or C1-6 alkyl; n is 0-1; p is 0-4; and q is 0. 2. The compound of claim 1, wherein R3 is SO2R12; and R12 is C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkenyl, pyrrolidinyl, piperazinyl, piperidinyl or morpholinyl. 3. The compound of claim 1, wherein one of R8 and R9 is (CR2)qY and the other is C1-6 alkyl; and n is 0. 4. The compound of claim 1, wherein said compound is selected from the group consisting of or pharmaceutically acceptable salts thereof. 5. The compound of claim 1, wherein said compound is 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine, or a pharmaceutically acceptable salt thereof. 6. A compound having Formula (1) or pharmaceutically acceptable salts thereof; wherein W is A1 and A4 are independently C; each A2 and A3 is C; R1 is halo or C1-6 alkyl; R2 is H; R3 is (CR2)0-2SO2R12; R4 is H, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; OR12, NR(R12), halo, nitro, SO2R12, (CR2)pR13 or X; R5, R5′, R7 and R10 are H; R6 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; OR12, NR(R12), halo, nitro, SO2R12, (CR2)pR13 or X; R8 and R9 are independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo or X; and provided one of R8 and R9 is X; R is H or C1-6 alkyl; X is (CR2)qY; Y is a 5-12 membered heterocyclic ring comprising N, O and/or S, and optionally substituted with C1-6 alkyl, hydroxylC1-C8alkyl, C1-C8alkoxyC1-C8alkyl or a 5-12 membered heterocyclic ring comprising N, O and/or S; and wherein Y is attached to A2 or A3 or both via a carbon atom of said heterocyclic ring when q in (CR2)qY is 0; R12 and R13 are independently 3-7 membered saturated or partially unsaturated carbocyclic ring, or a 5-7 membered heterocyclic ring comprising N, O and/or S; aryl or heteroaryl; or R12 is H, C1-6 alkyl; p is 0-4; and n and q are 0. 7. The compound of claim 6, wherein R3 is SO2R12 and R12 is C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkenyl, pyrrolidinyl, piperazinyl, piperidinyl or morpholinyl. 8. The compound of claim 6, wherein R6 is halo or OR12, wherein R12 is C1-6 alkyl. 9. The compound of claim 6, wherein said compound is selected from the group consisting of 67 5-chloro-N2-(2-isopropoxy-5-methyl-4-(1- methylpiperidin-4-yl)phenyl)-N4-[2- (propane-2-sulfonyl)phenyl]-pyrimidine-2,4-diamine; 69 5-chloro-N2-(2-isopropoxy-5-methyl-4-(1- (1-methylpiperidin-4-yl)piperidin-4- yl)phenyl)-N4-(2-(isopropylsulfonyl) phenyl)pyrimidine-2,4-diamine; 71 5-chloro-N2-(2-cyclobutoxy-5-methyl-4- (piperidin-4-yl)phenyl)-N4-(2- (isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine; 72 2-[4-(4-{5-Chloro-4-[2-(propane-2- sulfonyl)-phenylamino]-pyrimidin-2- ylamino}-5-isopropoxy-2-methyl-phenyl)- piperidin-1-yl]-ethanol; 73 5-chloro-N2-(2-isopropoxy-4-(1-(2- methoxyethyl)piperidin-4-yl)-5- methylphenyl)-N4-(2-(isopropylsulfonyl) phenyl)pyrimidine-2,4-diamine; 74 N2-(2-isopropoxy-5-methyl-4-(1- methylpiperidin-4-yl)phenyl)-N4-(2- (isopropylsulfonyl)phenyl)-5- methylpyrimidine-2,4-diamine; 75 5-chloro-N2-(2-isopropoxy-5-methyl-4-(1- methylpiperidin-4-yl)phenyl)-N4-(2- (propylsulfonyl)phenyl)pyrimidine-2,4-diamine; 77 5-chloro-N2-(2-isopropoxy-5-methyl-4-(1- methylpiperidin-4-yl)phenyl)-N4-(2- (pyrrolidin-1-ylsulfonyl)phenyl) pyrimidine-2,4-diamine; 82 5-chloro-N2-(2-isopropoxy-5-methyl-4-(1- methylpiperidin-4-yl)phenyl)-N4-(2- (methylsulfonyl)phenyl)pyrimidine-2,4-diamine; and 84 5-chloro-N4-(2-(cyclobutylsulfonyl)phenyl)-N2-(2- isopropoxy-5-methyl-4-(1- methylpiperidin-4-yl)phenyl)pyrimidine-2,4-diamine; or pharmaceutically acceptable salts thereof. 10. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier. 11. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 4 and a pharmaceutically acceptable carrier. 12. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 6 and a pharmaceutically acceptable carrier. 13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 9 and a pharmaceutically acceptable carrier. 14. A combination comprising a compound of claim 1, or pharmaceutically acceptable salts thereof, and a chemotherapeutic agent. 15. The combination of claim 14, for treating a cell proliferative disorder, wherein said cell proliferative disorder is lymphoma, osteosarcoma, melanoma, or a tumor of breast, renal, prostate, colorectal, thyroid, ovarian, pancreatic, neuronal, lung, uterine or gastrointestinal tumor, non-small cell lung cancer or neuroblastoma. 16. The compound of claim 6, wherein said compound is N2-(2-isopropoxy-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)-5-methylpyrimidine-2,4-diamine. 17. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 5 and a pharmaceutically acceptable carrier. 18. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 16 and a pharmaceutically acceptable carrier.