Patent ID: 6689754
Filing Date: 2004-02-10
Classification: A61K,C07D,C07K

Abstract:
or a pharmaceutically acceptable salt thereof, wherein is a 5-8 membered monocyclic heterocyclic ring, optionally unsaturated, containing 1 to 4 heteroatoms, selected from the group consisting of O, N and S, wherein X1 is selected from the group consisting of CH, CH2, N, NH, O and S; whereinY1 is selected from the group consisting of Nâ€”R2, O, and S; R2 is selected from the group consisting of H; alkyl; aryl; hydroxy; alkoxy; cyano; nitro; amino; alkenyl; alkynyl; amido; alkylcarbonyl; arylcarbonyl; alkoxycarbonyl; aryloxycarbonyl; haloalkylcarbonyl; haloalkoxycarbonyl; alkylthiocarbonyl; arylthiocarbonyl; acyloxymethoxycarbonyl; alkyl optionally substituted with one or more substitutent selected from the group consisting of lower alkyl, halogen, hydroxyl, haloalkyl, cyano, nitro, carboxyl, amino, alkoxy, aryl and aryl optionally substituted with one or more substituent selected from the group consisting of halogen, haloalkyl, lower alkyl, alkoxy, cyano, alkylsulfonyl, alkylthio, nitro, carboxyl, amino, hydroxyl, sulfonic acid, sulfonamide, aryl, fused aryl, monocyclic heterocycles, and fused monocyclic heterocycles; aryl optionally substituted with one or more substituent selected from the group consisting of halogen, haloalkyl, hydroxy, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, cyano, nitro, alkylthio, alkylsulfonyl, sulfonic acid, sulfonamide, a radical of the formula â€ƒamino, aryl, fused aryl, monocyclic heterocycles and fused monocyclic heterocycle; monocyclic heterocycles; and moncyclic heterocycles optionally substituted with one or more substitutent selected from the group consisting of halogen, haloalkyl, lower alkyl, alkoxy, amino, nitro, hydroxy, a radical of the formula â€ƒcyano, alkylthio, alkylsulfonyl, sulfonic acid, sulfonamide, aryl and fused aryl; or R2 taken together with R7 forms a 4-12 membered dinitrogen containing heterocycle optionally substituted with one or more substituent selected from the group consisting of lower alkyl, thioalkyl, alkylamino, hydroxy, keto, alkoxy, halo, phenyl, amino, carboxyl, carboxyl ester, spirodioxolane, and fused phenyl; or R2 taken together with R7 forms a 4-12 membered heterocycle, optionally unsaturated, containing one or more heteroatom selected from the group consisting of O, N and S; or R2 taken together with R7 forms a 5-9 membered heteroaromatic ring optionally substituted with one or more substituent selected from the group consisting of lower alkyl, phenyl, alkoxy and hydroxy; or R2 taken together with R7 forms a 5 membered heteroaromatic ring fused with a aryl or heteroaryl ring; wherein Y6 and Y7 are independently selected from the group consisting of O, N, and S; and R23 is selected from the group consisting of H, alkyl, aralkyl or aryl, R7 (when not taken together with R2) and R8 are independently selected from the group consisting of H; alkyl; alkenyl; alkynyl; aralkyl; amino; alkylamino; hydroxy; alkoxy; arylamino; amido; alkylcarbonyl; arylcarbonyl; alkoxycarbonyl; aryloxy; aryloxycarbonyl; haloalkylcarbonyl; haloalkoxycarbonyl; alkylthiocarbonyl; arylthiocarbonyl; acyloxymethoxycarbonyl; cycloalkyl; bicycloalkyl; aryl; acyl; benzoyl; alkyl optionally substituted with one or more substiuent selected from the group consisting of lower alkyl, halogen, hydroxy, haloalkyl, cyano, nitro, a radical of the formula â€ƒamino, alkoxy, thio, alkylthio, sulfonyl, aryl, aralkyl, aryl optionally substituted with one or more substituent selected from the group consisting of halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio, haloalkylthio, thio, hydroxy, cyano, nitro, a radical of the formula â€ƒaryloxy, amido, acylamino, amino, alkylamino, dialkylamino, trifluoroalkoxy, trifluoromethyl, sulfonyl, alkylsulfonyl, haloalkylsulfonyl, sulfonic acid, sulfonamide, aryl, fused aryl, moncyclic heterocycles, and fused moncyclic heterocycles; aryl optionally substituted with one or more substituent selected halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio, haloalkylthio, thio, hydroxy, cyano, nitro, a radical of the formula â€ƒaryloxy, amido, acylamino, amino, alkylamino, dialkylamino, trifluoroalkoxy, trifluoromethylsulfonyl, alkylsulfonyl, sulfonic acid, sulfonamide, aryl, fused aryl, moncyclic heterocycles, or fused moncyclic heterocycles; monocyclic heterocycles; monocyclic heterocycles optionally substituted with one or more substitutent selected from the group consisting of halogen, haloalkyl, lower alkyl, alkoxy, aryloxy, amino, nitro, hydroxy, a radical of the formula â€ƒcyano, alkylthio, alkylsulfonyl, aryl, and fused aryl; monocyclic and bicyclic heterocyclicalkyls; â€”SO2R10â€” wherein R10 is selected from the group consisting of alkyl, aryl and monocyclic heterocycles, all optionally substituted with one or more substituent selected from the group consisting of halogen, haloalkyl, alkyl, alkoxy, cyano, nitro, amino, acylamino, trifluoroalkyl, amido, alkylaminosulfonyl, alkylsufonyl, alkylsulfonylamino, alkylamino, dialkylamino, trifluoromethylthio, trifluoroalkoxy, trifluoromethylsulfonyl, aryl, aryloxy, thio, alkylthio, and monocyclic heterocycles; and â€ƒwherein R10 is defined above; or NR7 and R8 taken together form a 4-12 membered mononitrogen containing moncyclic or bicyclic ring optionally substituted with one or more substitutent selected from the group consisting of lower alkyl, a radical of the formula â€ƒaryl and hydroxy; and wherein said ring optionally contains a heteroatom selected from the group consisting of O, N, and S; R5 is selected from the group consisting of H, alkyl, alkenyl, alkynyl, benzyl, and phenethyl; or â€ƒwherein Y2 is selected from the group consisting of alkyl; cycloalkyl; bicycloalkyl; aryl; monocyclic heterocycles; alkyl optionally substituted with aryl which can also be optionally substituted with one or more substitutent selected from halo, haloalkyl, alkyl, nitro, hydroxy, alkoxy, aryloxy, aryl, or fused aryl; aryl optionally substituted with one or more substituent selected from the group consisting of halo, haloalkyl, hydroxy, alkoxy, aryloxy, aryl, fused aryl, nitro, methylenedioxy, ethylenedioxy, or alkyl; alkylnyl; alkenyl; â€”Sâ€”R9 and â€”Oâ€”R9â€” wherein R9 is selected from the group consisting of H; alkyl; aralkyl; aryl; alkenyl; and alkynyl; or R9 taken together with R7 forms a 4-12 membered mononitrogen and monosulfur or monooxygen containing heterocyclic ring optionally substituted with lower alkyl, hydroxy, keto, phenyl, carboxyl or carboxyl ester, and fused phenyl or R9 taken together with R7 is thiazole, oxazole, benzoxazole, or benzothiazole; and R5 and R7 are as defined above; or Y2 (when Y2 is carbon) taken together with R7 forms a 4-12 membered mononitrogen or dinitrogen containing ring optionally substituted with alkyl, aryl, keto or hydroxy; or where R2 and R7 taken together form a 5-8 membered dinitrogen containing heterocycle optionally substituted with one or more substituent selected from the group consisting of lower alkyl, hydroxy, alkoxy, keto, phenyl, or a radical of the formula â€ƒand R8 is selected from the group consisting of alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, haloalkylcarbonyl, haloalkoxycarbonyl, alkylthiocarbonyl, arylthiocarbonyl, or acyloxymethoxycarbonyl; and R5 is defined as above; or R2 and R7 taken together form a heteroaromatic ring such as imidazole or pyrimidone; Z1 is one or more substitutent selected from the group consisting of H; alkyl; hydroxy; alkoxy; aryloxy; halogen; haloalkyl; haloalkoxy; nitro; amino; alkylamino; acylamino; dialkylamino; cyano; alkylthio; alkylsulfonyl; a radical of the formula â€ƒtrihaloacetamide; acetamide; acyl; aryl; fused aryl; cycloalkyl; thio; monocyclic heterocycles; fused monocyclic heterocycles; and A, wherein A is defined above; V is selected from the group consisting of â€”Nâ€”(R6)â€” wherein R6 is selected from the group consisting of H; lower alkyl; cycloalkyl; aralkyl; aryl; and monocyclic heterocycles; or R6 taken together with Y, forms a 4-12 membered mononitrogen containing ring; Y, Y3, Z and Z3 are independently selected from the group consisting of hydrogen; alkyl; aryl; and cycloalkyl; or Y and Z taken together form a cycloalkyl; or Y3 and Z3 taken together form a cycloalkyl; n is an integer 1, 2, or 3; t is an integer 0, 1, or 2; p is an integer 0, 1, 2, or 3; R is Xâ€”R3 wherein X is selected from the group consisting of O, S and NR4, wherein R3 and R4 are independently selected from the group consisting of hydrogen; alkyl; alkenyl; alkynyl; haloalkyl; aryl; arylalkyl; sugars; steroids; polyalkylethers; alkylamido; alkyl N,N-dialkylamido; pivaloyloxymethyl; and in the case of the free acid, all pharmaceutically acceptable salts thereof; R1 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, a radical of the formula â€ƒhaloalkyl; cycloalkyl; moncyclic heterocycles; monocyclic heterocycles optionally substituted with one or more substituent selected from the group consisting of alkyl, halogen, haloalkyl, cyano, hydroxy, aryl, fused aryl, nitro, alkoxy, aryloxy, alkylsulfonyl, arylsulfonyl, sulfonamide, thio, alkylthio, a radical of the formula â€ƒamino, amido; alkyl optionally substituted with one or more of halo, haloalkyl, hydroxy, alkoxy, aryloxy, thio, alkylthio, alkynyl, alkenyl, alkyl, arylthio, alkylsulfoxide, alkylsulfonyl, arylsulfoxide, arylsulfonyl, cyano, nitro, amino, alkylamino, dialkylamino, alkylsulfonamide, arylsulfonamide, acylamide, a radical of the formula â€ƒsulfonamide, sulfonic acid, phosphonic acid derivatives, phosphinic acid derivatives, aryl, arylthio, arylsulfoxide, or arylsulfone all optionally substituted on the aryl ring with halo, alkyl, haloalkyl, cyano, nitro, hydroxy, a radical of the formula â€ƒalkoxy, aryloxy, amino, alkylamino, dialkylamino, amido, aryl, fused aryl, moncyclic heterocycles; and fused moncyclic heterocycles, moncyclic heterocyclicthio, moncyclic heterocyclicsulfoxide, and moncyclic heterocyclic sulfone, which can be optionally substituted with halo, haloalkyl, nitro, hydroxy, alkoxy, fused aryl, or alkyl; alkylcarbonyl, haloalkylcarbonyl, and arylcarbonyl; aryl optionally substituted in one or more positions with halo, haloalkyl, alkyl, alkoxy, aryloxy, methylenedioxy, ethylenedioxy, alkylthio, haloalkylthio, thio, hydroxy, cyano, nitro, acyloxy, a radical of the formula â€ƒcarboxyalkoxy; amido, acylamino, amino, alkylamino, dialkylamino, trifluoroalkoxy, trifluoromethylsulfonyl, alkylsulfonyl, sulfonic acid, sulfonamide, aryl, fused aryl, moncyclic heterocycles and fused heterocycles; and â€ƒwherein R7 and R8 are defined as above and provided that taken together with the nitrogen, R7 and R8 comprise an amino acid; and R11 is selected from the group consisting of H, alkyl, aralkyl, alkenyl, alkylnyl, haloalkyl or haloalkylnyl or R11 taken together with Y forms a 4-12 membered mononitrogen containing ring.