Compounds and compositions as protein kinase inhibitors

A method for treating a condition mediated by anaplastic lymphoma kinase, comprising administering to a cell or tissue system or to a mammalian subject, a therapeutically effective amount of a compound of 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;
• and optionally in combination with a second therapeutic agent, wherein said condition is an autoimmune disease, a transplantation disease, an infectious disease or a cell proliferative disorder.

A method for inhibiting anaplastic lymphoma kinase, comprising administering to a cell or tissue system or to a mammalian subject, a therapeutically effective amount of a compound of 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)gY;
• Y is a 5-12 membered heterocyclic ring comprising N, O and/or S, and optionally substituted with C1-6 alkyl, hydroxyl C1-C8alkyl, C1-C8alkoxy C1-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;
• thereby inhibiting said anaplastic lymphoma kinase.

A method for treating a condition mediated by anaplastic lymphoma kinase, comprising administering to a cell or tissue system or to a mammalian subject, a therapeutically effective amount of a compound of 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, hydroxyl C1-C8alkyl, C1-C8alkoxy C1-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;
• and optionally in combination with a second therapeutic agent, wherein said condition is an autoimmune disease, a transplantation disease, an infectious disease or a cell proliferative disorder.