Heteroaryl Dihydroindolones as Kinase Inhibitors

A compound represented by the formula:

• Wherein
• X is O or S;
• Y is O, S or NR3;
• Z is [C(R2)2]c;
• the ring system A is
• the ring system B represents a 5 or 6 membered aryl group III
• and is selected from the group consisting of
• R1 is selected from the group consisting of halogen, aryl, C1 to C8 alkyl, CF3, OCF3, OCF2H, S(O)fR2, (CR3R4)dC(O)OR2, O(CR3R4)eC(O)OR2, NR2(CR3R4)dC(O)R2, NR2(CR3R4)dC(O)OR2, OP(O)(OR2)2, OC(O)OR2, OCH2O, NR2(CH2)eN(R2)2, O(CH2)eN(R2)2, (CR3R4)dCN, O(CR3R4)eCN, (CR3R4)dAr, NR2(CR3R4)dAr, O(CR3R4)dAr, S(O)f(CR3R4)dAr, (CR3R4)dSO2R2, (CR3R4)dC(O)N(R2)2, NR2(CR3R4)dC(O)N(R2)2, O(CR3R4)dC(O)N(R2)2, S(O)f(CR3R4)eC(O)N(R2)2, (CR3R4)dOR2, NR2(CR3, R4)eOR2, O(CR3, R4)eOR2, S(O)f(CR3, R4)dOR2, C(O)(CR3R4)dR3, NR2C(O)(CR3R4)dR3, OC(O)(CR3R4)dN(R2)2, (CR3R4)dN(R2)2, NR2C(O)(CR3R4)dN(R2)2, OC(O)(CR3R4)dN(R2)2, (CR3R4)dR3, NR2(CR3R4)dR3, O(CR3R4)dR3, S(O)f(CR3R4)dR3, (CR3R4)dN(R2)2, NR2(CR3R4)eN(R2)2, O(CR3R4)eN(R2)2, S(O)f (CR3R4)dN(R2)2, N(R5)2, OR5, C(O)R5, S(O)fR5, C(O)ArNR2C(O)Ar, NR2ArNR2C(O)Ar, OArNR2C(O)Ar, SArNR2C(O)Ar, C(O)ArC(O)(NR2)2, OArC(O)(NR2)2, NR2ArC(O)(NR2)2, SArC(O)(NR2)2C(O)ArC(O)NR2Ar, OArC(O)NR2Ar, NR2ArC(O)NR2Ar and SArC(O)NR2Ar;
• R2 is selected from the group consisting of hydrogen, C1 to C8 alkyl, C1 to C8 alkenyl, C1 to C8 alkynyl, C1 to C4 alkylol, lower alkylphenyl, phenyl, (CR3R4)dAr, OC(O)R7, (CR3R4)dC(O)OR7, (CR3R4)dSO2R7, (CR3R4)dSO2N(R7)2 (CR3, R4)dOR7, (CR3R4)dOSO2R7, (CR3R4)dP(O)(OR7)2, (CR3R4)dR7, (CR3R4)eN(R7)2 and (CR3R4)eNR7C(O)N(R7)2 wherein N(R2)2 and N(R7)2 may form a 3-7 membered heterocyclic ring and [C(R2)2]c may form a 3-7 membered carbocyclic or heterocyclic ring, wherein said heterocyclic ring may be substituted with one or more of R3;
• R is selected from the group consisting of halogen, C1 to C8 alkyl, CF3, OCF3, OCF2H, (CR3R4)dCN, NR2(CR3R4)eCN, O(CR3R4)eCN, S(O)fR2, (CR3R4)dC(O)OR2, (CR3R4)dC(O)R2, (CR3R4)dC(OR2)2, NR2(CR3R4)dC(O)OR2, O(CR3R4)dC(O)OR2, S(O)f(CR3R4)dC(O)OR2, (CR3R4)dAr, NR2(CR3R4)dAr, O(CR3R4)dAr, S(O)f(CR3R4)dAr, (CR3R4)dSO2R2, NR2(CR3R4)dS(O)fR2, O(CR3R4)d S(O)fR2, S(O)f(CR3R4)eS(O)fR2, (CR3R4)dC(O)N(R2)2, NR2(CR3R4)dC(O)N(R2)2, O(CR3R4)dC(O)N(R2)2, S(O)f(CR3R4)eC(O)N(R2)2, (CR3, R4)dOR2, NR2 (CR3, R4)eOR2, O(CR3, R4)eOR2, S(O)f(CR3R4)dOR2, (CR3, R4)dOSO2R2, NR2 (CR3R4)dOSO2R2, O(CR3R4)eOSO2R2, S(O)f(CR3R4)dOSO2R2(CR3R4)dP(O)(OR2)2, NR2(CR3R4)dP(O)(OR2)2, O(CR3R4)dP(O)(OR2)2, S(O)f(CR3R4)eP(O)(OR2)2, C(O)(CR3R4)dR3, NR2C(O)(CR3R4)dR3, OC(O)(CR3R4)dN(R2)2, C(O)(CR3R4)dN(R2)2, C(O)NR2(CR3R4)eN(R2)2, NR2C(O)(CR3R4)dN(R2)2, OC(O)(CR3R4)dN(R2)2, (CR3R4)dR3, NR2(CR3R4)dR3, O(CR3R4)dR3, S(O)f(CR3R4)dR3, HNC(O)R2, HN—C(O)OR2, (CR3R4)dN(R2)2, NR2(CR3R4)eN(R2)2, O(CR3R4)eN(R2)2, S(O)f (CR3R4)dN(R2)2, OP(O)(OR2)2, OC(O)OR2, OCH2O, HN—CH═CH, —N(COR2)CH2CH2, HC═N—NH, N═CH—S, (CR3R4)dC═C(CR3R4)dR2, (CR3R4)dC═C(CR3R4)dOR2, (CR3R4)dC═C(CR3R4)dN(R2)2, (CR3R4)dCC(CR3R4)dR2,
• (CR3R4)dCC(CR3R4)eOR2, (CR3R4)dCC(CR3R4)eN(R2)2, (CR3R4)dC(O)(CR3R4)dR2, (CR3R4)dC(O)(CR3R4)dOR2 and (CR3R4)dC(O)(CR3R4)dN(R2)2 and (CR3R4)dR5;
• R3 and R4 may be selected from the group consisting of H, F, hydroxy, C1-C4 alkyl, (CR8R9)dOR8, (CR8R9)dO(CR8R9)eOR8, (CR8R9)dCOOR8 and (CR8R9)dN(R8)2 or CR3R4 may represent a carbocyclic or heterocyclic ring of from 3 to 6 carbons or, alternatively, (CR3R4)d and (CR3R4)e may form a 3-7 membered carbocyclic or heterocyclic ring;
• R5 is an aryl group or a substituted oxindole;
• R6 is selected from the group consisting of hydrogen, C1-C8 alkyl, hydroxymethyl and phenyl;
• R7 is selected from the group consisting of hydrogen, hydroxyl, F, C1 to C8 alkyl, C2 to C8 alkenyl, C2 to C8 alkynyl, C1 to C4 alkylol, lower alkylphenyl and phenyl;
• R8 and R9 are selected from the group consisting of hydrogen, hydroxyl, F, C2 to C8alkyl, C2 to C8 alkenyl, C2 to C8 alkynyl, C1 to C4 alkylol, lower alkylphenyl and phenyl;
• a is 0 or an integer of from 1 to 3;
• b is 0 or an integer of from 1 to 2;
• c is an integer of from 1 to 2;
• d is 0 or an integer of from 1 to 5;
• e is an integer of from 1 to 4;
• f is 0 or an integer of from 1 to 2, and further provided any of said alkyl or aryl radicals may be substituted with one or two halo, hydroxy, lower alkyloxy or lower alkyl amino radicals, including cycloalkylamino radicals and wherein the alkyl, or the cycloalkyl amino ring, can include an enchained oxygen, sulfur or additional nitrogen atom and may be substituted with one or two halo or lower alkyl radicals;
• and pharmaceutically acceptable salts thereof.