Patent ID: 6514966
Filing Date: 2003-02-04
Classification: A61P,C07D

Abstract:
A compound of the Formula I a prodrug thereof, or a pharmaceutically acceptable salt of said compound or of said prodrug;wherein Y is an aromatic five to eight membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen or an aromatic bicyclic ring consisting of two fused five to six membered rings, taken independently, optionally having one to four heteratoms selected independently from nitrogen, sulfur and oxygen; wherein said Y ring has a maximum of three substituents selected independently from Group I, Group II and Group III: Group I: said Y ring is optionally mono-, di-, or tri-substituted independently with nitro, amino, hydroxy, (C2-C6)alkenyl, (C1-C4)alkylthio, halo, cyano, (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkyloxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy or (C3-C6)cycloalkoxy, said (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkyloxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy and (C3-C6)cycloalkoxy moieties optionally substituted with one to nine fluorines; Group II: said Y ring is optionally mono-substituted with a four to seven membered saturated nitrogen containing ring optionally having one to two additional heteroatoms selected independently from sulfur, oxygen or nitrogen, said four to seven membered ring optionally mono- or di-substituted independently with (C1-C5)alkyl, said (C1-C5)alkyl optionally substituted with one to nine fluorines; or Group III: said Y ring is optionally mono-, or di-substituted independently with mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino, said mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino optionally mono-, di-, or tri-substituted independently on each (C1-C6)alkyl or (C3-C6)cycloalkyl with (C3-C6)cycloalkyl, hydroxy, (C1-C3)alkoxy, (C3-C6)cycloalkoxy, (C3-C6)cycloalkyl(C1-C3)alkoxy, cyano or fluoro; L and M are each independently carbon or nitrogen, with the proviso that L and M are not the same, wherein said carbon is bonded to an R3 ring through an R3 ring nitrogen; wherein R3 is a four to five membered saturated or partially saturated nitrogen containing ring optionally having one additional heteratom selected independently from sulfur, oxygen or nitrogen; wherein said additional optional R3 ring nitrogen is optionally mono-substituted with: 1) H or a T ring, optionally linked through (C1-C8)alkyl or carbonyl wherein said T ring is a partially saturated or fully unsaturated five to eight membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen or said T ring is a four to seven membered saturated ring having one to two heteroatoms selected independently from sulfur, oxygen or nitrogen or said T ring is an aromatic bicyclic ring consisting of two fused three to six membered rings, taken independently, optionally having one to four heteratoms selected independently from nitrogen, sulfur and oxygen; wherein said T ring is substituted with a maximum of three substituents selected independently from Group IV, Group V and Group VI: Group IV: said T ring is optionally mono-, di- or tri-substituted independently with nitro, amino, hydroxy, (C2-C6)alkenyl, (C1-C4)alkylthio, halo, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkyloxy, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, said (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkyloxy and (C3-C6)cycloalkoxy moieties optionally substituted with one to nine fluorines; Group V: said T ring optionally mono- or di-substituted independently with mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino wherein said mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino is optionally mono-, di-, or tri-substituted independently on each of said (C1-C6)alkyl or (C3-C6)cycloalkyl with (C3-C6)cycloalkyl, hydroxy, (C1-C3)alkoxy, (C3-C6)cycloalkoxy, (C3-C6)cycloalkyl(C1-C3)alkoxy, cyano or fluoro; Group VI: said T ring is optionally mono-substituted with a four to seven membered saturated nitrogen containing ring optionally having one to two additional heteroatoms selected independently from sulfur, oxygen or nitrogen linked to the aromatic T ring through nitrogen, said four to seven membered ring optionally mono-substituted with (C1-C5)alkyl, said (C1-C5)alkyl optionally substituted with one to nine fluorines; 2) (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl; wherein said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl is optionally substituted with one to nine fluorines and wherein said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl is optionally substituted with a maximum of three substituents selected independently from Group VII, Group VIII, Group IX and Group X: Group VII: said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl optionally mono-, di- or tri-substituted independently with mono-N- or di-N,N-(C1-C6)alkylaminocarbonyl, mono-N- or di-N,N-(C3-C6)cycloalkylaminocarbonyl, N-(C1-C6)alkyl-N-(C3-C6)cycloalkylaminocarbonyl, carboxy, nitro, amino, hydroxy, (C2-C6)alkenyl, (C1-C4)alkylthio, halo, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, or (C3-C6)cycloalkoxy, said mono-N- or di-N,N-(C1-C6)alkylaminocarbonyl, mono-N- or di-N,N-(C3-C6)cycloalkylaminocarbonyl, N-(C1-C6)alkyl-N-(C3-C6)cycloalkylaminocarbonyl, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, and (C3-C6)cycloalkoxy moieties optionally having one to nine fluorines; Group VIII: said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl optionally mono-substituted with a four to seven membered saturated nitrogen containing ring, linked through a ring nitrogen, said ring optionally having one to two additional heteroatoms selected independently from sulfur, oxygen or nitrogen, said four to seven membered ring optionally substituted with (C1-C5)alkyl, said (C1-C5)alkyl optionally substituted with one to nine fluorines; Group IX: said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl optionally mono-, di- or tri-substituted independently with mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino, said mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino optionally mono-, di-, or tri-substituted independently on each (C1-C6)alkyl or (C3-C6)cycloalkyl with (C3-C6)cycloalkyl, hydroxy, (C1-C3)alkoxy, (C3-C6)cycloalkoxy, cyano, or fluoro; Group X: said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl optionally mono-, di- or tri-substituted independently with (C1-C6)alkoxycarbonyl or (C1-C6)alkylformyl, said (C1-C6)alkoxycarbonyl or (C1-C6)alkylformyl optionally mono-, di- or tri-substituted independently with hydroxy, cyano, fluoro, (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkoxy or (C3-C6)cycloalkoxy said (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, C3-C6)cycloalkyl(C1-C6)alkoxy or (C3-C6)cycloalkoxy optionally substituted with one to nine fluorines; 3) (C1-C8)alkoxycarbonyl, (C3-C8)cycloalkoxycarbonyl, (C3-C8)cycloalkyl(C1-C8)alkoxycarbonyl, (C1-C8)alkylformyl, (C3-C8)cycloalkylformyl or (C3-C8)cycloalkyl(C1-C8)alkylformyl, said (C1-C8)alkoxycarbonyl, (C3-C8)cycloalkoxycarbonyl, (C3-C8)cycloalkyl(C1-C8)alkoxycarbonyl, (C1-C8)alkylformyl, (C3-C8)cycloalkylformyl or (C3-C8)cycloalkyl(C1-C8)alkylformyl optionally mono-, di- or tri-substituted independently with hydroxy, cyano, fluoro, (C1-C6)alkoxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkoxy or (C3-C6)cycloalkoxy, said (C1-C6)alkoxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkoxy or (C3-C6)cycloalkoxy optionally substituted with from one to nine fluorines; 4) sulfonyl, said sulfonyl optionally mono-substituted with amino, hydroxy, (C2-C8)alkenyl, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy, (C3-C8)cycloalkoxy, (C3-C8)cycloalkyl(C1-C8)alkyl or (C3-C8)cycloalkyl(C1-C8)alkyloxy said (C2-C8)alkenyl, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy, (C3-C8)cycloalkyl(C1-C8)alkyl, (C3-C8)cycloalkyl(C1-C8)alkyloxy and (C3-C8)cycloalkoxy moieties optionally substituted with one to nine fluoros; or said sulfonyl optionally mono-substituted with mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino,; wherein said mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino is optionally mono-, di-, or tri-substituted independently on each of said (C1-C6)alkyl or (C3-C6)cycloalkyl with (C3-C6)cycloalkyl, hydroxy, (C1-C3)alkoxy, (C3-C6)cycloalkoxy, cyano or fluoro; or said sulfonyl is optionally mono-substituted with a partially unsaturated or fully unsaturated five to eight membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen, a four to seven membered saturated ring having one to two heteroatoms selected independently from oxygen, sulfur or nitrogen or an aromatic bicyclic ring consisting of two fused three to six membered rings, taken independently, optionally having one to four heteratoms selected independently from nitrogen, sulfur and oxygen; wherein said ring is optionally mono-, di-, or tri-substituted independently with nitro, amino, hydroxy, (C2-C6)alkenyl, (C1-C4)alkylthio, halo, cyano, (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkyloxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, said (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkyloxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy and (C3-C6)cycloalkoxy moieties optionally substituted with one to nine fluorines; wherein said R3 ring is optionally mono-, or di-substituted independently on a single carbon or optionally mono-substituted independently on two separate carbons with R5 or R6 wherein R5 and R6 are independently 1) H, carboxy, oxo, amino, halo, cyano, hydroxy, nitro, (C2-C6)alkenyl, (C1-C4)alkylthio, (C1-C8)alkoxy, (C3-C8)cycloalkoxy, (C3-C8)cycloalkyl(C1-C8)alkoxy, said (C1-C8)alkoxy, (C3-C8)cycloalkyl(C1-C8)alkoxy and (C3-C8)cycloalkoxy substituents optionally substituted with one to nine fluorines or optionally mono- or di-substituted with hydroxy; 2) mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino, said mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino optionally mono-, di-, or tri-substituted independently on each (C1-C6)alkyl or (C3-C6)cycloalkyl with (C3-C6)cycloalkyl, hydroxy, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C3-C6)cycloalkyl(C1-C6)alkoxy, cyano or having one to nine fluorines; 3) (C1-C8)alkoxycarbonyl, (C3-C8)cycloalkoxycarbonyl, (C3-C8)cycloalkyl(C1-C8)alkoxycarbonyl, (C1-C8)alkylformyl, (C3-C8)cycloalkylformyl or (C3-C8)cycloalkyl(C1-C8)alkylformyl said (C1-C8)alkoxycarbonyl, (C3-C8)cycloalkoxycarbonyl, (C3-C8)cycloalkyl(C1-C8)alkoxycarbonyl, (C1-C8)alkylformyl, (C3-C8)cycloalkylformyl or (C3-C8)cycloalkyl(C1-C8)alkylformyl optionally mono-, di- or tri-substituted independently with hydroxy, cyano, fluoro, (C1-C6)alkoxy or (C1-C6)alkyl, said (C1-C6)alkoxy or (C1-C6)alkyl optionally substituted with from one to nine fluorines; 4) an X ring, optionally linked through (C1-C8)alkyl or carbonyl, wherein said X ring is a partially unsaturated or fully unsaturated five to eight membered ring optionally having one to two heteroatoms selected independently from oxygen, sulfur and nitrogen or said X ring is a four to seven membered saturated ring having one to three heteroatoms selected independently from oxygen, sulfur and nitrogen or said X ring is an aromatic bicyclic ring consisting of two fused three to six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen; wherein said X ring is optionally substituted with a maximum of three substituents selected independently from Group XI, Group XII or Group XIII Group XI: wherein said X ring is optionally mono-, di- or tri-substituted independently with nitro, amino, hydroxy, (C2-C6)alkenyl, (C1-C4)alkylthio, halo, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkoxy, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, said (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl(C1-C6)alkyl, (C3-C6)cycloalkyl(C1-C6)alkoxy, and (C3-C6)cycloalkoxy moieties optionally substituted with one to nine fluorines; Group XII: said X ring is optionally mono- or di-substituted independently with mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino; wherein said mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino is optionally mono-, di-, or tri-substituted independently on each of said (C1-C6)alkyl or (C3-C6)cycloalkyl with (C3-C6)cycloalkyl, hydroxy, (C1-C3)alkoxy, (C3-C6)cycloalkoxy, cyano or fluoro; or Group XIII: said X ring is optionally mono-substituted with a four to seven membered saturated nitrogen containing ring optionally having one to two additional heteroatoms selected independently from sulfur, oxygen or nitrogen linked to the aromatic X ring through nitrogen, said four to seven membered ring optionally substituted with (C1-C5)alkyl, said (C1-C5)alkyl optionally substituted with one to nine fluorines; 5) (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl, said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl optionally substituted with one to nine fluorines and said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl optionally substituted with a maximum of three substituents selected independently from Group XIV, XV, XVI or XVII; wherein Group XIV: said (C1-C8)alkyl, (C3-C8)cycloalkyl(C1-C8)alkyl or (C3-C8)cycloalkyl is optionally mono-, di- or tri-substituted independently with mono-N- or di-N,N-(C1-C6)alkylaminocarbonyl mono-N- or di-N,N-(C3-C6)cycloalkylaminocarbonyl, N-(C1-C6)alkyl-N-(C3-C6)cycloalkylaminocarbonyl, carboxy, nitro, amino, hydroxy, (C2-C6)alkenyl, (C1-C4)alkylthio, halo, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C1-C6)alkoxycarbonyl, said mono-N- or di-N,N-(C1-C6)alkylaminocarbonyl, mono-N- or di-N,N-(C3-C6)cycloalkylaminocarbonyl, N-(C1-C6)alkyl-N-(C3-C6)cycloalkylaminocarbonyl, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy and (C3-C6)cycloalkoxy moieties optionally substituted with one to nine fluorines; Group XV: said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl optionally mono-substituted with a four to seven membered saturated nitrogen containing ring, linked through a ring nitrogen, optionally having one to two additional heteroatoms selected independently from sulfur, oxygen or nitrogen, said four to seven membered ring optionally substituted with (C1-C5)alkyl, said (C1-C5)alkyl optionally substituted with one to nine fluorines; Group XVI: said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl optionally mono-, di- or tri-substituted independently with mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino, said mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino optionally mono-, di-, or tri-substituted independently on each (C1-C6)alkyl or (C3-C6)cycloalkyl with (C3-C6)cycloalkyl, hydroxy, (C1-C3)alkoxy, (C3-C6)cycloalkoxy, cyano or fluoro; Group XVII: said (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C8)alkyl optionally mono-, di- or tri-substituted independently with (C1-C6)alkoxycarbonyl or (C1-C6)alkylformyl, said (C1-C6)alkoxycarbonyl or (C1-C6)alkylformyl optionally mono-, di- or tri-substituted independently with hydroxy, cyano, fluoro, (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl or (C3-C6)cycloalkoxy said (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl or (C3-C6)cycloalkoxy optionally substituted with one to nine fluorines; 6) sulfonyl, said sulfonyl optionally mono-substituted with amino, hydroxy, (C2-C8)alkenyl, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl, (C3-C8)cycloalkyl(C1-C8)alkoxy, (C1-C8)alkoxy, (C3-C8)cycloalkoxy, said (C2-C8)alkenyl, (C3-C8)cycloalkyl(C1-C8)alkyl, (C3-C8)cycloalkyl(C1-C8)alkoxy, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C1-C8)alkoxy or (C3-C8)cycloalkoxy moieties optionally substituted with one to nine fluorines or said sulfonyl optionally mono-substituted with mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino; wherein said mono-N- or di-N,N-(C1-C6)alkylamino, mono-N- or di-N,N-(C3-C6)cycloalkylamino or N-(C1-C6)alkyl-N-(C3-C6)cycloalkylamino is optionally mono-, di-, or tri-substituted independently on each of said (C1-C6)alkyl or (C3-C6)cycloalkyl with (C3-C6)cycloalkyl, hydroxy, (C1-C3)alkoxy, (C3-C6)cycloalkoxy, cyano or fluoro.