Patent ID: 6420385
Filing Date: 2002-07-16
Classification: A61P,C07D

Abstract:
A compound of formula or a pharmaceutically acceptable salt thereof, whereinX is O, S or NR5; â€ƒprovided that the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in â€”VC(R)Wâ€” is 0-3; R1 and R2 are each independently â€”Y or â€”Zâ€”Y, and R3 is â€”Zâ€”Y or a hydrogen radical; provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each â€”Y and â€”Zâ€”Y is 0-3; wherein each Z is independently a (1) 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; (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 Y is independently a (1) hydrogen radical; (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, wherein the aryl, heteroaryl, heterocyclyl and cycloalkyl radicals are optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; and wherein each R20 is independently a (1) alkyl, alkenyl or alkynyl radical optionally substituted by 1-3 radicals of â€”CO2R23, amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, N-(alkoxycarbonyl)-N-(alkyl)amino, aminocarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, aralkoxy, aralkylthio, aralkylsulfonyl, cycloalkyl, heterocyclyl, aryl or heteroaryl radicals, wherein the aryl, heteroaryl, heterocyclyl and cycloalkyl radicals are 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 aryl, heteroaryl and heterocyclyl radicals are 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 hydrogen, alkyl, aryl, heteroaryl, aralkyl or heteroaralkyl radical, wherein the aryl and heteroaryl radicals are optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; and 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 (1) R11 is other than a 4-pyridyl, 4-pyrimidinyl, 4-quinolyl or 6-isoquinolinyl radical optionally substituted by 1-2 substituents; and (2) 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 a (1) alkyl, alkenyl or alkynyl radical optionally substituted by 1-3 radicals of â€”NR31R31, â€”CO2R23, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, aralkoxy, aralkylthio, aralkylsulfonyl, heterocyclyl, aryl or heteroaryl radicals, wherein the aryl, heteroaryl and heterocyclyl radicals are 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 aryl, heteroaryl, heterocyclyl and cycloalkyl radicals are 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 radical of heterocyclyl, aryl or heteroaryl, wherein the aryl, heteroaryl and heterocyclyl radicals are optionally substituted by 1-3 radicals of amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, cyano, alkyl or haloalkyl; and provided that (a) when R11 is aryl, then R12 is other than aryl or thienyl; (b) when X is NH, R11 is phenyl and R12 is pyridyl, then R2 is other than cyano; (c) when X is O, R1 is 2-benzimidazolyl, thienyl, phenyl, methylphenyl or dichlorophenyl, and R12 is phenyl, methylphenyl or methoxyphenyl, then R11 is other than 4-hydroxy-2-thiazolyl, 5-methyl-1-phenyl-1H-pyrazol-3-yl, 5-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-3-yl, 5-(4-methoxyphenyl)-1H-pyrazol-3-yl or 5-(4-methoxyphenyl)-3-isoxazolyl; and (d) when X is NH, R11 is 2-benzimidazolyl or 2-benothiazolyl, and R12 is furyl or chlorophenyl, then R1 is other than thienyl or naphthyl.