Patent ID: 6541467
Filing Date: 2003-04-01
Classification: A61K,C07D,C07K

Abstract:
A compound of the formulaR1â€”X-Lac-Jâ€”E wherein(a) X is selected from the group consisting of â€”S(O)2â€”, â€”N(Râ€²)â€”S(O)2â€”, â€”C(&boxH;O)â€”, â€”OC(&boxH;O)â€”, â€”N(Râ€²)C(&boxH;O)â€”, and a direct link, wherein Râ€² is selected from hydrogen, alkyl of 1 to about 4 carbon atoms, aryl of about 6 to about 14 carbon atoms and aralkyl of about 6 to about 16 carbon atoms; (b) R1 is selected from the group consisting of: (1) alkyl of 1 to about 12 carbon atoms which is optionally substituted with Y1 and/or Y2, (2) alkyl of i to about 3 carbon atoms substituted with cycloalkyl of about 3 to about 8 carbon atoms which is optionally mono-, di-, or tri-substituted on the ring with Y1, Y2 and/or Y3, (3) cycloalkyl of 3 to about 15 carbon atoms, which is optionally mono-, di-, or tri-substituted on the ring with Y1, Y2 and/or Y3, (4) heterocycloalkyl of 4 to about 10 ring atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from the group consisting of oxygen, nitrogen, and S(O)i, wherein i is 0, 1 or 2, which is optionally mono-, di-, or tri-substituted on the ring with Y1, Y2 and/or Y3, (5) heterocyclo of 4 to about 10 ring atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from the group consisting of oxygen, nitrogen, and S(O)i, including â€ƒwherein â€ƒis a 5 to 7 member heterocycle of 3 to 6 ring carbon atoms, where G is â€”CH2â€”, â€”Oâ€”, â€”S(&boxH;O)â€”, â€”S(O)2â€” or â€”Sâ€”, which is optionally mono-, di-, or tri-substituted on the ring carbons with Y1, Y2 and/or Y3, (6) alkenyl of about 2 to about 6 carbon atoms which is optionally substituted with cycloalkyl of about 5 to about 8 carbon atoms, which is optionally mono-, di-, or tri-.substituted on the ring carbons with Y1, Y2 and/or Y3, (7) aryl of about 6 to about 14 carbon atoms which is optionally mono-, di- or tri-substituted with Y1, Y2 and/or Y3 (8) heteroaryl of about 5 to about 14 ring atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from oxygen, nitrogen, and sulfur, and which is optionally mono-, di-, or tri-substituted with Y1, Y2 and/or Y3, (9) aralkyl of about 7 to about 15 carbon atoms which is optionally substituted on the alkyl chain with hydroxy or halogen and mono-, di-, or tri-substituted in the aryl ring with Y1, Y2 and/or Y3, (10) heteroaralkyl of 5 to 14 ring atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from oxygen, nitrogen, and sulfur, and which is optionally substituted on the alkyl chain with hydroxy or halogen and optionally mono-, di- or tri-substituted on the ring with Y1, Y2 and/or Y3, (11) aralkenyl of about 8 to about 16 carbon atoms which is optionally mono-, di-, or tri-substituted on the aryl ring with Y1, Y2 and/or Y3, (12) heteroaralkenyl of 5 to 14 ring atoms with the ring atoms selected from carbon and heteroatoms, wherein the heteroatoms are selected from oxygen, nitrogen, and sulfur, and which is optionally mono-, di- or tri-substituted on the ring with Y1, Y2 and/or Y3, (17) fused carbocyclic alkyl of about 5 to about 15 carbon atoms, (18) difluoromethyl or perfluoroalkyl of 1 to about 12 carbon atoms, (19) perfluoroaryl of about 6 to about 14 carbon atoms, (20) perfluoraralkyl of about 7 to about 15 carbon atoms, and (21) hydrogen when X is a direct link; â€ƒwherein (i) each Y1, Y2 and Y3 is independently selected from the group consisting of halogen, cyano, nitro, tetrazolyl optionally substituted with alkyl of 1 to about 6 carbon atoms, guanidino, amidino, methylamino, methylguanidino, â€”CF3, â€”CF2CF3, â€”CH(CF3)2, â€”C(OH)(CF3)2, â€”OCF3, â€”OCF2CF3, â€”OCF2H, â€”OC(O)NH2, â€”OC(O)NHZ1, â€”OC(O)NZ1Z2, â€”NHC(O)Z1, â€”NHC(O)NH2, â€”NHC(O)NHZ1, â€”NHC(O)NZ1Z2, â€”C(O)OH, â€”C(O)OZ1, â€”C(O)NH2, â€”C(O)NZ1Z2, â€”P(O)3H2, â€”P(O)3(Z1)2, â€”S(O)3H, â€”S(O)pZ1, â€”Z1, â€”OZ1, â€”OH, â€”NH2, â€”NHZ1, â€”NZ1Z2, N-morpholino, and â€”S(O)p(CF2)qCF3, wherein p is 0, 1 or 2, q is an integer from 0 to 5, and Z1 and Z2 are independently selected from the group consisting of alkyl of 1 to about 12 carbon atoms, aryl of about 6 to about 14 carbon atoms, heteroaryl of about 5 to about 14 atoms having 1 to about 9 carbon atoms, aralkyl of about 7 to about 15 carbon atoms, and heteroaralkyl of about 5 to about 14 ring atoms having about 3 to about 9 carbon atoms, or (ii) Y1 and Y2 are selected together to be â€”O[C(Z3)(Z4)]rOâ€” or â€”O[C(Z3)(Z4)]r+1â€”, wherein r is an integer from 1 to 4 and Z3 and Z4 are independently selected from the group consisting of hydrogen, alkyl of 1 to about 12 carbon atoms, aryl of about 6 to about 14 carbon atoms, heteroaryl of about 5 to about 14 ring atoms having 1 to about 9 carbon atoms, aralkyl of about 7 to about 15 carbon atoms, and heteroaralkyl of about 5 to about 14 ring atoms having about 3 to about 9 carbon atoms; (c) Lac is â€ƒwherein (i) n is 2; and (ii) R2 and R3 are independently selected from the group consisting of hydrogen, alkyl of 1 to about 6 carbon atoms, cycloalkyl of 3 to about 8 carbon atoms, and aryl of about 6 to about 14 carbon atoms; and (d) J is selected from wherein R4 is selected from the group consisting of hydrogen, alkyl of 1 to about 6 carbon atoms; cycloalkyl of 3 to about 8 carbon: atoms and aryl of about 6 to about 14 carbon atoms; R5a and R5b are independently selected from hydrogen, fluoro, chloro and alkyl of 1 to about 3 carbon atoms; R6 is hydrogen, alkyl of 1 to about 3 carbon atoms, â€”C(&boxH;O)R7a, or â€”CH2OR7b; R7a is alkyl of 1 to about 6 carbon atoms, alkoxy of 1 to about 6 carbon atoms, amino, alkylamino of 1 to about 6 carbon atoms, or dialkylamino of 2 to about 12 carbon atoms; R7b is hydrogen, acyl, or alkyl of 1 to about 6 carbon atoms; and Q7, Q8 and Q9 are independently selected from C(R5a), N, S and O, provided that (i) Q7, Q8 and Q9 are not all C(R5a) and (ii) only one of Q7, Q8 and Q9 can be O or S; and (e) E is a six membered heterocyclic ring having two ring nitrogen atoms and the remainder of the ring atoms carbon atoms which is substituted with â€ƒon a ring carbon and is substituted with R10 and R11 on different ring carbons wherein (1) R8 is selected from hydrogen, alkyl of about 1 to about 4 carbon atoms, cycloalkyl of 3 to about 7 carbon atoms, â€”(CF2)kCF3, â€”OR12 and â€”C(&boxH;O)R12 wherein R12 is H or alkyl of 1 to about 4 carbon atoms and k is 0, 1, 2 or 3; (2) R9 is selected from hydrogen and alkyl of 1 to about 4 carbon atoms; (3) alternatively R8 and R9 are taken together to give a divalent radical of the formula â€”(CH2)wâ€” wherein w is 3, 4 or 5; and (4), R10 and R11 are independently selected from hydrogen, alkyl of 1 to about 4 carbon atoms, alkyl of 1 to about 4 carbon atoms substituted with alkoxy of 1 to about 3 carbon atoms, alkoxy of 1 to about 8 carbon atoms, halogen, trifluoromethyl, â€”OC(R13)(R14)â€”C(&boxH;O)â€”R15 wherein R13 and R14 are independently selected from hydrogen or alkyl of 1 to about 4 carbon atoms, R15 is hydroxy, alkoxy of 1 to about 4 carbon atoms or â€”N(R16)(R17) wherein R16 and R17 are independently hydrogen or alkyl of 1 to about 4 carbon atoms; and pharmaceutically acceptable salts thereof.