Patent ID: 6440973
Filing Date: 2002-08-27
Classification: A61P,C07D

Abstract:
A compound of formula or a pharmaceutically acceptable salt thereof, whereinX1 is N; X2 is CH or CR2; X3 is CH or CR3; and X4 is N; wherein R2 and R3 are each independently â€”Zâ€”Y, provided that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each â€”Zâ€”Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 and R3 is 0-4; wherein each Z is independently a (1) bond; (2) alkyl, alkenyl or alkynyl radical optionally substituted by (a) 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano or halo, and (b) 1-2 radicals of heterocyclyl, aryl or heteroaryl optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl; (3) heterocyclyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; or (4) aryl or heteroaryl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl; each Y is independently a (1) hydrogen radical, provided Z is other than a bond; (2) halo, cyano or nitro radical; (3) â€”C(O)â€”R20, â€”C(O)â€”OR21, â€”C(O)â€”NR5R21 or â€”C(NR5)â€”NR5R21 radical; (4) â€”OR21, â€”Oâ€”C(O)â€”R21, â€”Oâ€”C(O)â€”NR5R21 or â€”Oâ€”C(O)â€”NR22â€”S(O)2â€”R20 radical; (5) â€”SR21, â€”S(O)â€”R20, â€”S(O)2â€”R20, â€”S(O)2â€”NR5R21, â€”S(O)2â€”NR22â€”C(O)â€”R21, â€”S(O)2â€”NR22â€”C(O)â€”OR20 or â€”S(O)2â€”NR22â€”C(O)â€”NR5R21 radical; or (6) â€”NR5R21, â€”NR22â€”C(O)â€”R21, â€”NR22â€”C(O)â€”OR20, â€”NR22â€”C(O)â€”NR5R21, â€”NR22â€”C(NR5)â€”NR5R21, â€”NR22â€”S(O)2â€”R20 or â€”NR22â€”S(O)2â€”NR5R21 radical; wherein each R5 is independently a (1) hydrogen radical; (2) alkyl, alkenyl or alkynyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, hydroxy, alkoxy, alkylthio, cyano or halo; or (3) aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl or cycloalkylalkyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; and wherein each R20 is independently an (1) alkyl, alkenyl or alkynyl radical optionally substituted by 1-3 radicals of (a) â€”CO2R23, amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, N-(alkoxycarbonyl)-N-(alkyl)amino, aminocarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano or halo radicals or (b) aralkoxy, aralkylthio, aralkylsulfonyl, cycloalkyl, heterocyclyl, aryl or heteroaryl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkanoyl, alkoxycarbonyl, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; (2) heterocyclyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkoxycarbonyl, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; or (3) aryl or heteroaryl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkoxycarbonyl, hydroxy, alkoxy, alkylthio, cyano, halo, azido, alkyl or haloalkyl; each R21 is independently hydrogen radical or R20; each R22 is independently a (1) hydrogen radical; (2) alkyl radical optionally substituted by a radical of heterocyclyl, aryl or heteroaryl, wherein the heterocyclyl, aryl or heteroaryl radical is optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; or (3) heterocyclyl, aryl or heteroaryl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; and each R23 is independently a (a) hydrogen or alkyl radical, or (b) aryl, heteroaryl, aralkyl or heteroaralkyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; and R10 is a hydrogen, R30, â€”C(O)â€”R29, â€”C(O)â€”OR30, â€”C(O)â€”NR31R32, â€”S(O)2â€”R30 or â€”S(O)2â€”NR31R32 radical; R11 and R12 are each independently an aryl or heteroaryl radical optionally substituted by 1-3 radicals of (1) R30; (2) halo or cyano radicals; (3) â€”C(O)â€”R30, â€”C(O)â€”OR29, â€”C(O)â€”NR31R32 or â€”C(NR31)â€”NR31R32 radicals; (4) â€”OR29, â€”Oâ€”C(O)â€”R29, â€”Oâ€”C(O)â€”NR31R32 or â€”Oâ€”C(O)â€”NR33â€”S(O)2â€”R30 radicals; (5) â€”SR29, â€”S(O)â€”R30, â€”S(O)2â€”R30, â€”S(O)2â€”NR31R32, â€”S(O)2â€”NR33â€”C(O)â€”R30, â€”S(O)2â€”NR33â€”C(O)â€”OR30 or â€”S(O)2â€”NR33â€”C(O)â€”NR31R32 radicals; or (6) â€”NR31R32, â€”NR33â€”C(O)â€”R29, â€”NR33â€”C(O)â€”OR30, â€”NR33â€”C(O)â€”NR31R32, â€”NR33â€”C(NR31)â€”NR31R32, â€”NR33â€”S(O)2â€”R30 or â€”NR33â€”S(O)2â€”NR31R32 radicals; provided that R11 and R12 are not both phenyl, 4-methoxyphenyl or 4-chlorophenyl radicals; and the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals substituted on each of R11 and R12 is 0-1; wherein each R30 is independently an (1) alkyl, alkenyl or alkynyl radical optionally substituted by 1-3 radicals of (a) â€”NR31R31, â€”CO2R23, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano or halo radicals or (b) aralkoxy, aralkylthio, aralkylsulfonyl, heterocyclyl, aryl or heteroaryl radicals optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; (2) heterocyclyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; or (3) aryl or heteroaryl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl; each R29 is independently hydrogen radical or R30; each R31 and R32 are each independently a (1) hydrogen radical; (2) alkyl radical optionally substituted by an cycloalkyl, aryl, heterocyclyl or heteroaryl radical, wherein the cycloalkyl, aryl, heterocyclyl or heteroaryl radical is optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; or (3) aryl, heteroaryl, heterocyclyl or cycloalkyl radical optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; and wherein each R33 is independently a (1) hydrogen radical; or (2) alkyl radical optionally substituted by a heterocyclyl, aryl or heteroaryl radical, wherein the heterocyclyl, aryl or heteroaryl radical is optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; and wherein heterocyclyl is a radical of a monocyclic or bicyclic saturated heterocyclic ring system having 5-8 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally partially unsaturated or benzo-fused and optionally substituted by 1-2 oxo or thioxo radicals; aryl is a phenyl or naphthyl radical; and heteroaryl is radical of a monocyclic or bicyclic aromatic heterocyclic ring system having 5-6 ring members per ring, wherein 1-3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally henzo-fused or saturated C3-C4-carbocyclic-fused.