Arylsulfonamide derivatives

A compound of formula I and pharmaceutically acceptable salts thereof:

• wherein
• A is O, CO, S, NRd, or CRbRc;
• D is COR4, C(O)NRdR4, C(O)OR4, SO2R4′, SO2NRdR4;
• X, Y and Z are independently a ring carbon atom or a ring nitrogen atom, with the proviso that 0-3 X, 0-3 Y and 0-3 Z are ring nitrogen atoms;
• R1a and R1b are independently selected from (1) H, (2) halogen, (3) C1-6alkyl optionally substituted with 1-5 groups independently selected from halogen, nitro, cyano, CORa, CO2Ra, C(O)NRdRe, ORa, OC(O)Ra, SRa, SO2Rf, S(O)Rf, NRdRe, NRdC(O)Ra and NRdSO2Rf, (4) C(O)Ra, (5) CO2Ra, (6) C(O)NRdRe, (7) ORa, (8) OC(O)Ra, (9) OC(O)NRdRe, (10) NRdRe, (11) NRdC(O)Ra, (12) NRdC(O)ORa, (13) NRdC(O)NRdRe, (14) NRdSO2Rf, (15) SRa, (16) S(O)Rf, (17) SO2Rf, (18) SO2NRdRe, (19) CN, (20) NO2, (21) optionally substituted aryl, (22) optionally substituted heteroaryl, (23) optionally substituted heterocyclyl, (24) optionally substituted aryl-C1-6alkyl, (25) optionally substituted heteroaryl-C1-6alkyl, and (26) optionally substituted heterocyclyl-C1-6alkyl;
• wherein the substituents for aryl, heteroaryl, heterocyclyl, aralkyl, heteroaralkyl and heterocyclylalkyl are 1 to 3 groups independently selected from halogen, cyano, nitro, ORa, NRdRe, NRdC(O)Ra, NRdSO2Rf, OC(O)Ra, NRdC(O)2Ra, SRa, SO2Rf, oxo (for heterocyclyl and heterocyclylalkyl), C(O)Ra, C(O)2Ra, C1-4 alkyloxy, aryl, aryl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, C3-6 cycloalkyl and C1-4 alkyl optionally substituted with 1 to 5 halogen atoms, or
• R1a, R1b and adjacent carbon atoms to which they are attached together form a saturated, partially unsaturated or aromatic 5- or 6-membered ring containing 0 to 2 heteroatoms selected from N, N-Rg, O and S;
• R2a and R3a are independently selected from (1) H, (2) halogen, (3) ORa, (4) NRdRe, (5) CN, (6) NO2, (7) CO2Ra, (8) CORa, and (9) C1-4 alkyl optionally substituted with 1 to 5 halogen atoms,
• R4 is selected from (1) H, (2) C1-6alkyl optionally substituted with 1 to 5 groups independently from halogen, nitro, cyano, C3-6cycloalkyl, CORa, CO2Ra, C(O)NRdRe, ORa, OC(O)Ra, SRa, SO2Rf, S(O)Rf, NRdRe, NRdC(O)Ra, NRdSO2Rf, and NRdC(O)2Ra, (3) optionally substituted C3-6cycloalkyl, (4) CORa, (5) COORa, (6) optionally substituted aryl, (7) optionally substituted heteroaryl, (8) optionally substituted heterocyclyl, (9) optionally substituted aryl-C1-6alkyl, (10) optionally substituted heteroaryl-C1-6alkyl, and (11) optionally substituted heterocyclyl-C1-6alkyl;
• wherein the substituents for cycloalkyl, aryl, heteroaryl, heterocyclyl, aralkyl, heteroaralkyl and heterocyclylalkyl are 1 to 3 groups independently selected from halogen, cyano, nitro, ORa, NRdRe, NRdC(O)Ra, NRdSO2Rf, OC(O)Ra, NRdC(O)2Ra, SRa, SO2Rf, oxo (for heterocyclyl and heterocyclylalkyl), C(O)Ra, C(O)2Ra, C1-4 alkyloxy, aryl optionally substituted with 1 or 2 halogen atoms, aryl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, C3-6 cycloalkyl and C1-4 alkyl optionally substituted with 1 to 5 halogen atoms;
• R4′ is a group selected from R4 except R4′ is not H;
• Ra is (1) H, (2) C1-6 alkyl optionally substituted with 1 to 5 groups independently selected from halogen, cyano, nitro, OH, C1-4 alkyloxy and C3-6 cycloalkyl, (3) C3-6 cycloalkyl, (4) optionally substituted aryl, (5) optionally substituted heteroaryl, (6) optionally substituted heterocyclyl, (7) optionally substituted aryl-C1-6alkyl, (8) optionally substituted heteroaryl-C1-6alkyl, and (9) optionally substituted heterocyclyl-C1-6alkyl;
• wherein the substituents for aryl, heteroaryl, heterocyclyl, aralkyl, heteroaralkyl and heterocyclylalkyl are 1 to 3 groups independently selected from halogen, cyano, nitro, ORg, NRdRe, NRdC(O)Rg, NRdSO2Rf, OC(O)Rg, NRdC(O)2Rg, SRg, SO2Rf, oxo (for heterocyclyl and heterocyclylalkyl), C(O)Rga, C(O)2Rg, C1-4 alkyloxy, aryl, aryl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, C3-6 cycloalkyl and C1-4 alkyl optionally substituted with 1 to 5 halogen atoms;
• Rb and Rc are independently selected from H, halogen, or C1-4alkyl optionally substituted with 1 to 5 halogen atoms;
• Rd and Re are independently selected from (1) H, (2) C1-4alkyl, optionally substituted with 1 to 5 groups independently selected from halogen, amino, mono-C1-4alkylamino, di-C1-4alkylamino, and SO2Rf, (3) aryl-C1-6alkyl optionally substituted with 1 to 3 groups selected from halogen, cyano, nitro, OH, C1-4 alkyloxy, C3-6 cycloalkyl and C1-4 alkyl optionally substituted with 1 to 5 halogen atoms, (4) heteroaryl-C1-6alkyl optionally substituted with 1 to 3 groups selected from halogen, cyano, nitro, OH, C1-4 alkyloxy, C3-6 cycloalkyl and C1-4 alkyl optionally substituted with 1 to 5 halogen atoms,and (5) C3-6 cycloalkyl, or
• Rd and Re, or Rd and R4, or Rd and R4′, together with the atom or atoms to which they are attached, complete a 4- to 8-membered saturated, partially saturated or aromatic ring optionally containing 1 to 3 heteroatoms independently selected from N, NRg, O, S, and SO2, and said ring being optionally fused to a benzene or a 5- or 6-membered heteraromatic ring, and optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro, ORg, oxo, C3-6 cycloalkyl, aryl, aryl-C1-4alkyl, heteroaryl, NRgRg, NRgCORg, NRgCO2Rg and C1-4 alkyl optionally substituted with 1 to 5 halogen atoms;
• Rf is selected from (1) C1-4 alkyl optionally substituted with 1 to 5 halogen atoms, (2) C1-4 alkyloxy, and (3) aryl optionally substituted with 1 to 3 groups selected from halogen, cyano, nitro, OH, C1-4 alkyloxy, C3-6 cycloalkyl and C1-4 alkyl optionally substituted with 1 to 5 halogen atoms;
• Rg is selected from (1) H, (2) C1-4alkyl, (3) aryl, (4) aryl-C1-6alkyl, (5) C(O)2C1-4alkyl and (6) C(O)C1-4alkyl;
• with the proviso that when each occurrence of X, Y and Z is a ring carbon atom, R1a and R1b are each hydrogen or chlorine, and R2a and R2b are each hydrogen, then D is not NHC(O)C1-6alkyl;
• with the further proviso that the following compound is excluded: