Claims for Patent: 8,399,450

Summary for Patent: 8,399,450

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, Wenshuo Lu, Bei Chen, Tetsuo Uno, Yunho Jin, Tao Jiang
Assignee:	Novartis AG
Application Number:	US13/172,357
Patent Claims:	1. 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; B and C are independently an optionally substituted 5-7 membered carbocyclic ring, aryl, heteroaryl or heterocyclic ring containing N, O or S; Z1, Z2 and Z3 are independently NR11, C═O, CR—OR, (CR2)1-2 or ═C—R12; R1 is halo or C1-6 alkyl; R2 is H; R3 is SO2R12 or cyano; R4, R7 and R10 are independently H; R, R5 and R5′ are independently H or C1-6 alkyl; R6 is —OR12; one of R8 and R9 is (CR2)qY and the other is C1-6 alkyl; R11 is H, C1-6 alkyl, C2-6 alkenyl, (CR2)pCO1-2R, (CR2)pOR, (CR2)pR13, (CR2)pNRR12, (CR2)pCONRR12 or (CR2)pSO1-2R12; R12 and R13 are independently an optionally substituted 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; Y is an optionally substituted 3-12 membered carbocyclic ring, a 5-12 membered aryl, or a 5-12 membered heteroaryl comprising N, O and/or S and attached to A2 or A3 or both via a carbon atom of said heteroaryl n is 4; p is 0-4; and q is 0. 2. The compound of claim 1, wherein R12 is C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkenyl, pyrrolidinyl, piperazinyl, piperidinyl or morpholinyl. 3. The compound of claim 1, wherein R6 is —O(C1-6 alkyl). 4. The compound of claim 1, wherein R5 and R5′ are H. 5. The compound of claim 1, wherein said compound is of Formula (2): or pharmaceutically acceptable salts thereof; wherein R1 is halo or C1-6 alkyl; R2 is H; R6 is isopropoxy or methoxy; Y is an optionally substituted C3-7 cycloalkyl, C3-7 cycloalkenyl, or phenyl; or Y is pyridyl, pyrazolyl, isoxazolyl, imidazolyl, thiazolyl, or benzimidazolyl, each of which is attached to the phenyl ring via a carbon atom; and R3, R4, R8, R9 and n are as defined in claim 1. 6. The compound of claim 1, wherein said compound is of Formula (3A) or (3B): wherein B and C together form Z1, Z2 and Z3 together form or tautomers thereof; R1 is halo or C1-6 alkyl; R2 is H; and R6 is isopropoxy or methoxy. 7. The compound of claim 6, wherein each R11 is (CR2)pCO1-2R, (CR2)pOR, (CR2)pR13, (CR2)pNRR12 or (CR2)pCONRR12; R and R12 are independently H or C1-6 alkyl; and R13 is an optionally substituted piperidinyl, azetidiyl, tetrahydropyranyl, cyclohexyl, morpholinyl, pyrrolidinyl, heptamethyleneimine, octamethyleneimine, a bicyclic amine or diamine derivative, quinuclidin-3-yl, 8-methyl-8-aza-bicyclo[3.2.1]oct-6-yl], or 9-methyl-9-aza-bicyclo[4.2.1]nonan-7-yl. 8. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier. 9. A combination comprising a compound of claim 1, or pharmaceutically acceptable salts thereof, and a chemotherapeutic agent. 10. The compound of claim 1, wherein said compound is selected from the group consisting of or a pharmaceutically acceptable salt thereof. 11. The compound of claim 5, wherein said compound is selected from the group consisting of or a pharmaceutically acceptable salt thereof. 12. The compound of claim 1, wherein said compound is selected from the group consisting of or pharmaceutically acceptable salts thereof. 13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 10 and a pharmaceutically acceptable carrier. 14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 11 and a pharmaceutically acceptable carrier. 15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 12 and a pharmaceutically acceptable carrier.