Patent ID: 6525067
Filing Date: 2003-02-25
Classification: A61P,C07D

Abstract:
A compound having Formula VII: wherein:the dashed line in the figure represents alternating single and double bonds; A is CR7; B is â€”C(R2)(&boxH;NY1R1), â€”(Y3)â€”C(R2)(&boxH;NY1R1), â€”NR16R2, â€”NHCR16R2, â€”SCHR16R2, â€”CHR16R2, â€”C(OH)R16R2, â€”CHR16(OR12), â€”C(F)R16R2, â€”C(OMe)R16R2, â€”CR16(&boxH;CR2R1), â€”C(N(C1-C4 alkyl)R2)(&boxH;NY1R1), â€”Y3C(Y2R2)(&boxH;NY1R1), or â€”V1â€”V2; Q and U are carbon; V1 is (C0-C1 alkylene), O, S, NH, or â€”N(C1-C4 alkylene); V2 is a five to eight membered carbocyclic ring wherein one or two of the carbocyclic ring carbons may optionally and independently be replaced by O, S, N, or NZ3, and the ring optionally consists of one to three double bonds, further wherein the ring is optionally substituted with from one to two R22 substituents and wherein the ring or R22 consists of the moiety C&boxH;Nâ€”Y1â€”(C1-C4 alkylene); X2 is S or O; Y1, Y2, and Y3 are each independently O, S, NH, or â€”N(C1-C4 alkyl); wherein: D and E are independently selected from CR4; K is CR6; G is carbon; and wherein the ring consisting of D, E, K, G, in Formula VII is an aromatic carbocyclic ring having alternating single and double bonds; Z2 is hydrogen or C1-C4 alkyl; Z3 is hydrogen, C1-C4 alkyl, or benzyl; Z4 is N, CH, or C(C1-C2 alkyl) when single bonded to both adjacent ring atoms, and Z4 is carbon when double bonded to either adjacent ring atom; Ar is C6-C10 aryl or 5-10 membered heteroaryl, wherein Ar is optionally substituted with from one to four R13 substituents, and wherein two adjacent R13 substituents optionally form a five to seven membered ring structure fused to Ar, which five to seven membered ring may be further substituted with from one to four independently selected R13 substituents, and which five to seven membered ring optionally consists of one to three double bonds and one to three heteroatoms selected from O, S, N, and NZ3; R1 is H, C1-C6 alkyl, C6-C10 aryl, 5-10 membered heteroaryl, (C1-C6 alkylene)-(C6-C10 aryl), (C1-C6 alkylene)-(5-10 membered heteroaryl), C3-C8 cycloalkyl, (C1-C6 alkylene)-(C3-C8 cycloalkyl), C3-C8 spiroalkyl, C3-C8 heteroarylalkyl, or (C1-C4 alkylene)-(C3-C8 heteroarylalkyl), wherein each of said R1 groups is optionally substituted with one or two substituents independently selected from hydroxy, fluoro, chloro, bromo, iodo, C1-C6 alkyl, alkoxy, CF3, â€”C(&boxH;O)Oâ€”(C1-C4 alkyl), â€”OC(&boxH;O)(C1-C4 alkyl), C1-C6 alkyl, C3-C8 cycloalkyl, â€”OC(&boxH;O)N(C1-C4 alkyl)(C1-C2 alkyl), â€”NHCO(C1-C4 alkyl), â€”COOH, â€”COO(C1-C4 alkyl), â€”CONH2, â€”CONH(C1-C4 alkyl), â€”CON(C1-C4 alkyl)(C1-C2 alkyl), â€”S(C1-C4 alkyl), CN, â€”NO2, â€”SO(C1-C4 alkyl), â€”SO2(C1-C4 alkyl), â€”SO2NH(C1-C4 alkyl) â€”SO2N(C1-C4 alkyl)(C1-C2 alkyl), and NR17R18, wherein each of the alkyl moieties of said R1 groups that consist of three or more carbons optionally consists of one or two double or triple bonds and wherein each of the C1-C2 alkyl moieties in said RI groups optionally consists of one double or triple bond, provided that when Y1 is S, or O, and Y1 is attached to R1, then R1 is not H; R2 is H, C1-C6 alkyl, C6-C10 aryl, 5-10 membered heteroaryl, (C1-C6 alkylene)-Y1â€”(C1-C6 alkyl), (C1-C6 alkylene)-(C6-C10 aryl), (C1-C6 alkylene)-(5-10 membered heteroaryl), C3-C8 cycloalkyl, (C1-C6 alkylene)-(C3-C8 cycloalkyl), wherein each of said R2 groups is optionally substituted with from one to three substituents independently selected from chloro, fluoro and C1-C4 alkyl, or with one substituent selected from hydroxy, bromo, iodo, C1-C6 alkoxy, â€”OC(&boxH;O)(C1-C6 alkyl), â€”OC(&boxH;O)NH(C1C4 alkyl), â€”OC(&boxH;O)N(C1-C4 alkyl)(C1-C2 alkyl), â€”S(C1-C6 alkyl), amino, â€”NH(C1-C2 alkyl), â€”N(C1-C2 alkyl)(C1-C4 alkyl), â€”N(C1-C4 alkyl)-COâ€”(C1-C4 alkyl), â€”NHCO(C1-C4 alkyl), â€”COOH, â€”COO(C1-C4 alkyl), â€”CONH(C1-C4 alkyl), â€”CON(C1-C4 alkyl)(C1-C2 alkyl), â€”SH, â€”CN, â€”NO2, â€”SO(C1-C4 alkyl), â€”SO2(C1-C4 alkyl), â€”SO2NH(C1-C4 alkyl) and â€”SO2N(C1-C4 alkyl)(C1-C2 alkyl), provided that when Y2 is S, or O, then R2 is not H; R3 is hydrogen, C1-C4 alkyl, â€”O(C1-C4 alkyl), chloro, fluoro, bromo, iodo, CF3, (C1-C2 alkylene)O(C1-C2 alkyl), (C1-C2 alkylene)-OH, â€”S(C1-C4 alkyl) or â€”SO2(C1-C4 alkyl); R4 and R6 are each independently hydrogen, OH, (C1-C6 alkyl), or one of R4 or R6 is hydrogen, (C1-C4 alkyl), CF3, CH2CF3, CF2CF3, and the other is â€”CO(C1-C4 alkyl), â€”S(C1-C2 alkyl), â€”O(C1-C4 alkyl), or â€”NH(C1-C4 alkyl), wherein adjacent substituents at D and E may optionally form a 5 to 6 membered carbocyclic or heterocyclic ring fused to the bicyclic ring consisting of D and E, wherein said heterocyclic ring consists of 1 to 3 heteroatoms, and wherein CR4R6 optionally forms a C3-C5 carbocyclic ring wherein one member of said C3-C5 carbocyclic ring may optionally be replaced with O; R5 is hydrogen, C1-C6 alkyl, fluoro, chloro, bromo, iodo, hydroxy, cyano, amino, (C1-C2 alkylene)-OH, (C1-C2 alkylene)-O(C1-C4 alkyl), â€”CH2OCF3, CF3, â€”CH2SMe, â€”S(C1-C3 alkyl), nitro, â€”O(C1-C4 alkyl), â€”N(C1-C4 alkyl)(C1-C2 alkyl), â€”S(C1-C4 alkyl), â€”C(&boxH;O)(C1-C4 alkyl), â€”C(&boxH;NOH)(C1-C4 alkyl), â€”C(&boxH;NOâ€”(C1-C4 alkyl))(C1-C4 alkyl), â€”C(&boxH;O)H, â€”C(&boxH;O)O(C1-C4alkyl), â€”CONR17R18, wherein each of the C1-C4 alkyl moieties of R5 optionally consists of one double or triple bond and is optionally substituted with one substituent selected from hydroxy, amino, NHCOCH3, NH(C1-C2 alkyl), and N(C1-C2 alkyl)2; R7 is hydrogen, C1-C4 alkyl, chloro, fluoro, iodo, bromo, hydroxy, â€”O(C1-C4 alkyl), â€”C(&boxH;O)(C1-C4 alkyl), â€”C(&boxH;O)O(C1-C4 alkyl), â€”OCF3, â€”CF3, â€”CH2OH or â€”CH2O(C1-C2 alkyl; R8, R9, and R10 are independently hydrogen or C1-C4 alkyl; R11 and R12 are independently hydrogen, trifluoromethyl or methyl, or one of R11 and R12 is cyano and the other is hydrogen or methyl; R13 is fluoro, chloro, iodo, bromo, C1-C6 alkyl, C3-C8 cycloalkyl, (C1-C4 alkylene)-(C3-C8 cycloalkyl), â€”O(C1-C6 alkyl), â€”O(C3-C8 cycloalkyl), â€”Oâ€”(C1-C4 alkylene)-(C3-C8 cycloalkyl), formyl, OH, OCF3, OCHF2, (C1-C4 alkylene)-OH, (C1-C4 alkylene)-Oâ€”(C1-C2 alkyl), â€”CN, â€”CF3, CHF2, NO2, â€”NH2, â€”NH(C1-C4 alkyl), â€”N(C1-C2 alkyl)(C1-C6 alkyl), â€”OC(&boxH;O)(C1-C4 alkyl), (C1-C4 alkylene)-Oâ€”(C1-C4 alkyl), â€”S(C1-C6 alkyl), (C1-C4 alkylene)-Sâ€”(C1-C4 alkyl), â€”C(&boxH;O)O(C1-C4 alkyl), â€”C(&boxH;O)(C1-C4 alkyl), (C0-C2 alkylene)-C(&boxH;Nâ€”O(C0-C4 alkyl)), â€”COOH, â€”SO2NH(C1-C4 alkyl), â€”SO2N(C1-C2 alkyl)(C1-C4 alkyl), â€”SO2NH2, â€”NHSO2(C1-C4 alkyl), â€”S(C1-C6 alkyl), â€”SO2(C1-C6 alkyl), â€”CONR17R18, (C1-C2 alkylene)NR17R1 and C3-C8 carbocyclic ring in which one or two carbon atoms may be replaced with O, S, or N to form a heterocyclic ring and wherein said carbocyclic or heterocyclic ring may optionally consist of one to three double bonds, and wherein each of the C1-C4 alkyl and C1-C6 alkyl moieties in said R13 group optionally has one or two double bonds, and said C1-C4 alkylene and said C1-C6 alkyl in said R13 group is optionally substituted with C1-C4 alkyl or F; R14 and R15 are independently selected from H, C1-C4 alkyl, â€”CH2(C3-C8 cycloalkyl), and C3-C8 cycloalkyl; R16 is â€”R19â€”C(&boxH;Nâ€”Y1R1)â€”R20, wherein each alkyl or alkylene group in said R16 group optionally consists of one or two double or triple bonds; R17 and R18 are independently H, C1-C6 alkyl, or C3-C8 heterocycloalkyl; or NR17R18 forms a C4-C6 heterocyclo ring which is optionally substituted with hydrogen, C1-C6 alkyl, CONH2, CO[N(C0-C4 alkyl)(C0-C4 alkyl)], or C4-C8 heterocycloalkyl; R19 is C1-C6 alkylene, (C1-C6 alkylene)-Y1-(alkylene), CO, CS, SO, SO2, wherein said alkylene is optionally substituted with hydroxy, fluoro, chloro, bromo, iodo, C1-C4 alkoxy, CF3, CHF2, Oâ€”CF3, OCHF2, â€”C(&boxH;O)Oâ€”(CC4 alkyl), â€”OC(&boxH;O)(C1-C4 alkyl), â€”OC(&boxH;O)N(C1-C4 alkyl)(C1-C2 alkyl), â€”NHCO(C1-C4 alkyl), â€”COOH, â€”COO(C1-C4 alkyl), â€”CONH(C1-C4 alkyl), â€”CON(C1-C4 alkyl)(C1-C2 alkyl), â€”S(C1-C4 alkyl), CN, â€”NO2, â€”SO(C1-C4 alkyl), â€”SO2(C1-C4 alkyl), â€”SO2NH(C1-C4 alkyl) or â€”SO2N(C1-C4 alkyl)(C1-C2 alkyl); R20 is hydrogen, C1-C4 alkyl, (C0-C4 alkylene)-NR17R18, or (C1-C6 alkylene)-Gâ€²-R21, wherein Gâ€² is oxygen or sulfur; R21 is hydrogen, CF3, or C1-C4 alkyl; and R22 is hydrogen, C1-C4 alkyl, â€”O(C1-C4 alkyl), chloro, fluoro, bromo, iodo, CF3, (C1-C2 alkylene)O(C1-C2 alkyl), (C1-C2 alkylene)-OH, â€”S(C1-C4 alkyl), â€”SO2(C1-C4 alkyl); or C&boxH;Nâ€”Y1â€”(C1-C4 alkyl); and wherein, unless otherwise indicated, heteroaryl consists of one to five heteroatoms selected from S, SO, SO2, N, and NZ3 and consists of no Sâ€”S, â€”Oâ€”, or Sâ€”O bonds, and heterocyclyl consists of one to four heteroatoms selected from O, S, N, or NZ3, and one to three double bonds, and alkyl, alkoxy, spiroalkyl, cycloalkyl, and heterocycloalkyl optionally consist of from one to three double or triple bonds; or a pharmaceutically acceptable salt or prodrug of the compound.