Compounds and compositions as protein kinase inhibitors

1. A compound having Formula (1):

or pharmaceutically acceptable salts thereof; wherein

W is

A 1 and A 4 are independently C;

each A 2 and A 3 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;

Z 1 , Z 2 and Z 3 are independently NR 11 , C═O, CR—OR, (CR 2 ) 1-2 or ═C—R 12 ;

R 1 is halo or C 1-6 alkyl;

R 2 is H;

R 3 is SO 2 R 12 or cyano;

R 4 , R 7 and R 10 are independently H;

R, R 5 and R 5′ are independently H or C 1-6 alkyl;

R 6 is —OR 12 ;

one of R 8 and R 9 is (CR 2 ) q Y and the other is C 1-6 alkyl;

R 11 is H, C 1-6 alkyl, C 2-6 alkenyl, (CR 2 ) p CO 1-2 R, (CR 2 ) p OR, (CR 2 ) p R 13 , (CR 2 ) p NRR 12 , (CR 2 ) p CONRR 12 or (CR 2 ) p SO 1-2 R 12 ;

R 12 and R 13 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 R 12 is H or C 1-6 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 A 2 or A 3 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 R 12 is C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkenyl, pyrrolidinyl, piperazinyl, piperidinyl or morpholinyl.

3. The compound of claim 1 , wherein R 6 is —O(C 1-6 alkyl).

4. The compound of claim 1 , wherein

R 5 and R 5′ are H.

5. The compound of claim 1 , wherein said compound is of Formula (2):

or pharmaceutically acceptable salts thereof;

wherein R 1 is halo or C 1-6 alkyl;

R 2 is H;

R 6 is isopropoxy or methoxy;

Y is an optionally substituted C 3-7 cycloalkyl, C 3-7 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

R 3 , R 4 , R 8 , R 9 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

Z 1 , Z 2 and Z 3 together form

or tautomers thereof;

R 1 is halo or C 1-6 alkyl;

R 2 is H; and

R 6 is isopropoxy or methoxy.

7. The compound of claim 6 , wherein each R 11 is (CR 2 ) p CO 1-2 R, (CR 2 ) p OR, (CR 2 ) p R 13 , (CR 2 ) p NRR 12 or (CR 2 ) p CONRR 12 ;

R and R 12 are independently H or C 1-6 alkyl; and

R 13 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.