Patent ID: 6613942
Filing Date: 2003-09-02
Classification: A61P,C07C,C07D

Abstract:
A compound of formula I: wherein:R1 and R2 together form a valence bond; R3 is hydrogen or lower alkyl and R4 is hydrogen; n is 0, 1, 2 or 3; m is 0 or 1; X is >C&boxH;O, A is wherein:R8 is halogen, â€”CN, â€”F3, â€”OCF3, â€”OCH2CF3, â€”NO2, â€”OCOR13, â€”OSO2R13, -Olower alkyl, â€”Oaryl, â€”NR11R12, lower alkyl, aryl, â€”SCF3, â€”SR11, â€”CHF2, â€”OCHF2, â€”OSO2R11, â€”CONR11R12, â€”CH2OR11, â€”CH2NR11R12, â€”OCOR11, â€”CO2R13 or â€”OSO2CF3, and R9 is hydrogen, halogen, â€”CN, â€”CF3, â€”OCF3, â€”OCH2CF3, â€”NO2, â€”OR11, â€”NR11R12, lower alkyl, aryl, â€”SCF3, â€”SR11, â€”CHF2, â€”OCHF2, â€”OSO2R11, â€”CONR11R12, â€”CH2OR11, â€”CH2NR11R12, â€”OCOR11, â€”CO2R13 or â€”OSO2CF3, or R8 and R9 together form a bridge â€”OCH2Oâ€” or â€”OCH2CH2Oâ€”; wherein R11 and R12 independently are hydrogen, â€”COR13, â€”SO2R13, lower alkyl or aryl; wherein R13 is hydrogen, lower alkyl, aryl-lower alkyl or aryl; and R10 is hydrogen, lower alkyl, aryl-lower alkyl or aryl; B is wherein:R14 and R15 independently are hydrogen, halogen, â€”CN, â€”CF3, â€”OCF3, â€”O(CH2)lCF3, â€”NO2, â€”OR16, â€”NR16R17, lower alkyl, aryl, aryl-lower alkyl, â€”SCF3, â€”SR16, â€”CHF2, â€”OCHF2, â€”OCF2CHF2, â€”OSO2CF3, â€”CONR16R17, â€”(CH2)lCONR16R17, â€”O(CH2)lCONR16R17, â€”(CH2)lCOR16, â€”(CH2)lCOR16, â€”(CH2)lOR16, â€”O(CH2)lOR16, â€”(CH2)lNR16R17, â€”O(CH2)lNR16R17, â€”OCOR16, â€”CO2R18, â€”O(CH2)lCO2R18, â€”O(CH2)lCN, â€”O(CH2)lCl, or R14 and R15 together form a bridge â€”O(CH2)lOâ€” or â€”(CH2)lâ€”; wherein l is 1, 2, 3 or 4; R16 and R17 independently are hydrogen, â€”COR18, â€”SO2R18, lower alkyl, aryl, or R16 and R17 together form a cyclic alkyl bridge containing from 2 to 7 carbon atoms; wherein R18 is hydrogen, lower alkyl, aryl or aryl-lower alkyl; W is CR19&boxH;; Y is â€”CR20&boxH;; Z is â€”CR21&boxH;; and V is â€”CR22&boxH;; wherein: R19, R20, R21 and R22 independently are hydrogen, halogen, â€”CN, â€”CF3, â€”OCF3, â€”OCH2CF3, â€”NO2, â€”OR24, â€”NR24R25, lower alkyl, aryl, aryl-lower alkyl, â€”SCF3, â€”SR24, â€”CHF2, 13 OCHF2, â€”OCF2CHF2, â€”OSO2CF3, â€”CONR24R25, â€”CH2CONR24R25, â€”OCH2CONR24R25, â€”CH2OR24, â€”CH2NR24R25, â€”OCOR24 or â€”COR2R24, or R19 and R20, R20 and R21, or R21 and R22 together form a bridge â€”OCH2Oâ€”; wherein R24 and R25 independently are hydrogen, â€”COR26, â€”SO2R26, lower alkyl, aryl or aryl-lower alkyl; and wherein R26 is hydrogen, lower alkyl, aryl or aryl-lower alkyl; K is wherein:R3a, R3b, R4a and R4b independently are hydrogen, halogen, â€”CN, â€”CF3, â€”OCF3, â€”OCH2CF3, â€”NO2, â€”OR24n, â€”NR24nR25a, lower alkyl, aryl, aryl-lower alkyl, â€”SCF3, â€”SR24n, â€”CHF2, â€”OCH2, â€”OCF2CHF2, â€”OSO2CF3, â€”CONR24nR25a, â€”CH2CONR24aR25n, â€”OCH2CONR24aR25n, â€”CH2OR24n, â€”CH2NR24aR25n, â€”OCOR24n or â€”CO2R24n; wherein R24n and R25a independently are hydrogen, â€”COR26n, â€”SO2R26a, lower alkyl, aryl or aryl-lower alkyl; wherein R26a is hydrogen, lower alkyl, aryl or aryl-lower alkyl; or R3n and R3b, R4n and R4b, or R3n and R4b together form a bridge â€”(CH2)iâ€”; wherein i is 1, 2, 3 or 4; a, b, c and d independently are 0, 1, 2, 3 or 4; e, f and p independently are 0 or 1; q is 0, 1 or 2; and L and M independently are â€”Oâ€”, â€”Sâ€”, â€”CH&boxH;CHâ€”, â€”Câ‰¡Câ€”, â€”NR5aâ€”, â€”CH2NR5aâ€”, â€”COâ€”, â€”OCOâ€”, â€”COOâ€”, â€”CONR5aâ€”, â€”CONR5bâ€”, â€”NR5nCOâ€”, â€”SOâ€”, â€”SO2â€”, â€”OSO2â€”, â€”SO2NR5aâ€”, â€”NR5nSO2â€”, â€”NR5aCON5bâ€”, â€”CONR5aNR5bâ€”, â€”NR5aCSNR5bâ€”, â€”OCONR5bâ€”, â€”CH2CONR5bâ€”, â€”OCH2CONR5b, â€”P(O)(OR5a)Oâ€”, â€”NR5aC(O)Oâ€” or wherein R5a and R5b independently are hydrogen, lower alkyl, â€”OH, â€”(CH2)kOR6n, â€”COR6n, â€”(CH2)kâ€”CH(OR6n)z, â€”(CH2)kâ€”CN, â€”(CH2)kâ€”NR6aR6b, aryl, aryl-lower alkyl, â€”(CH2)Eâ€”COOR43 or â€”(CH2)Eâ€”CF3; wherein k is 1, 2, 3 or 4; R6a and R6b independently are hydrogen, lower alkyl, aryl or aryl-lower alkyl; g is 0, 1, 2, 3 or 4; R43 is hydrogen or lower alkyl; Gâ€³ is â€”OCH2COâ€”, â€”CH2COâ€”, â€”COâ€” or a valence bond; and Eâ€³ is â€”CH2â€”, â€”CH2CH2â€”, â€”CH&boxH;CHâ€”, â€”CH2NHâ€” or â€”CH2CH2NHâ€”; D is hydrogen, wherein:r is 0 or 1; s is 0, 1, 2 or 3; E, Eâ€², F, G and Gâ€² independently are â€”CHR38â€”, >C&boxH;O, >NR39, â€”Oâ€” or â€”Sâ€”; Fâ€² is >CR38â€” or >Nâ€”; Yâ€²is â€”N&boxH; or â€”CR32&boxH;; Zâ€² is â€”N&boxH; or CR33&boxH;; Vâ€² is â€”N&boxH; or â€”CR34&boxH;; Wâ€² is â€”N&boxH; or â€”CR35&boxH;; and Qâ€² is â€”NR36â€”, â€”Oâ€” or â€”Sâ€”; wherein: R27, R28, R32, R33, R34 and R35 independently are hydrogen, halogen, â€”CN, â€”CF3, â€”O(CH2)yCF3, â€”(CH2)yNHCOCF3, â€”NO2, lower alkyl, aryl aryl-lower alkyl, â€”SCF3, â€”SR29, â€”CHF2, â€”OCHF2, â€”OCF2CHF2, â€”OSO2R29, â€”OSO2CF3, â€”(CH2)yCONR29R30, â€”O(CH2)yCONR29R30, â€”(CH2)yOR29, â€”(CH2)yNR29R30, â€”OCOR29, â€”COR29 or â€”CO2R29; or R27 and R28, R32 and R33, R33 and R34, or R34 and R35 together form a bridge â€”O(CH2)yOâ€”; wherein y is 0, 1, 2, 3 or 4; and R29 and R30 independently are hydrogen, â€”COR31, â€”CO2R31, â€”SO2R31, lower alkyl, aryl or aryl-lower alkyl; wherein R31 is hydrogen, lower alkyl, aryl or aryl-lower alkyl; R36 and R39 independently are hydrogen, lower alkyl, aryl or aryl-lower alkyl; and R38 is hydrogen, â€”OR40, â€”NR40R41, lower alkyl, aryl, aryl-lower alkyl, â€”SCF3, â€”SR40, â€”CHF2, â€”OCHF2, â€”OCF2CHF2, â€”CONR40R41, â€”(CH2)xCONR40R41, â€”O(CH2)xCONR40R41, â€”(CH2)xOR40, â€”(CH2)xNR40R41, â€”OCOR40 or â€”CO2R40; wherein x is 1, 2, 3 or 4; R40 and R41 independently are hydrogen, â€”COR42, â€”SO2R42, lower alkyl, aryl or aryl-lower alkyl; wherein R42 is hydrogen, lower alkyl, aryl or aryl-lower alkyl; as well as any optical or geometric isomer or tautomeric form thereof including mixtures of these or a pharmaceutically acceptable salt thereof.