Patent ID: 6627656
Filing Date: 2003-09-30
Classification: A61P,C07C,C07D

Abstract:
A method of treating a prostaglandin E mediated disease which comprises administering to a mammalian patient in need of such treatment or prevention a compound of formula I: wherein:R is a group Ar as defined hereinafter; R1 is hydrogen, hydroxy, C1-6alkyl, C1-6alkoxy, X(CH2)pAr, or a methylenedioxy group attached to two adjacent ring carbon atoms; R2 is â€”(CH2)xC(O)N(R4)S(O)yR5, â€”(CH2)xS(O)yN(R4)C(O)R5, â€”(CH2)xC(O)N(R4)C(O)R5, â€”(CH2)xS(O)yN(R4)S(O)yR5, â€”(CH2)xCO2R4, or tetrazol-5-yl optionally substituted by C1-6alkyl; R3 is X(CH2)pAr or X(CH2)pR4 or a group of formula (a): Ar is a group of formula (b) or (c): â€ƒor Ar is naphthyl, which may be unsubstituted or substituted by one or more R7 or R8 groups; A is C&boxH;O or (C(R4)2)m; each B is â€”CH2â€”; R4 is hydrogen or C1-6alkyl, with the proviso that when R7 or R9 is Xâ€”(CR4)pâ€”OR4, X is (CH2)pand p is 0 then R4 is not C1-6alkyl; R5 is hydrogen or C1-10alkyl or Ar, both of which may be unsubstituted or substituted by one or two Cl, F, Br, hydroxy, XC1-5alkyl, C1-5alkyl, NO2, tetrazol-5-yl optionally substituted by C1-6alkyl, or R5 is N(R4)2; R6 is R10, CO2R11, CO2C(R10)2O(CO)XR11, PO3(R11)2, SO2NR11R10, NR11 SO2R10, CONR11SO2R10, SO3R11, S(O)qR11, S(O)qN(R11)C(O)R10, S(O)qN(R11)S(O)qR10, C(O)N(R11)C(O)R10, N(R11)C(O)R10, N(R11)2, N(R11)C(O)NR11, P(O)(OR11)R11, CN, â€”CO2(CH2)mC(O)N(R4)2, C(R10)2N(R11)2, C(O)N(R4)2, OR4or tetrazolyl optionally substituted by C1-6 alkyl, with the proviso that when R7 or R9 is â€”Xâ€”(CH2)pâ€”R6, p is 0 and X is (CH2)p then R6 is not S(O)qR11; R7 and R9 are independently R10, OH, C1-8 alkoxy, S(O)qR10, Br, F, I, Cl, CF3, NO2, NHCOR4, R12CO2R11, â€”Xâ€”R13â€”Y, â€”X(CR4)pR4, S(CH2)pCO2H, (CH2)pXâ€”R13 â€”, X(CH2)pCONR11 SO2R10, (CH2)pXCONR11SO2R10 or X(CH2)pR6 wherein each methylene group within â€”X(CH2)qR6 may be unsubstituted or substituted by one or two â€”(CH2)pAr groups; R8 is hydrogen, R10, OH, C1-5alkoxy, S(O)qR10, N(R4)2, Br, F, I, Cl or NHCOR4wherein the C1-5 alkoxy may be unsubstituted or substituted by OH, methoxy or halogen; R10 is hydrogen, Ar, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, all of which may be unsubstituted or substituted by one or more OH,CH2OH, N(R4)2 or halogen; or R10 is N(R4)2; R11 is independently hydrogen, C1-10alkyl, C2-10alkenyl or C2-8alkynyl, all of which may be unsubstituted or substituted by one or more OH, N(R4)2, CO2R14, halogen or XC1-5alkyl; or R11 is (CH2)pAr; R12 is divalent Ar, C1-10alkylene, C1-10alkylidene, C2-10alkenylene, C2-10alkynylene, all of which may be unsubstituted or substituted by one or more of OH, CH2OH, N(R4)2or halogen; R13 is selected from the group consisting of: (1) a bond, (2) when R13 is a linking group, selected from the group consisting of C1-10alkylene, C1-10alkenylene, C1-10alkylidene, C1-10alkynylene, all of which may be linear or branched, or phenylene, all of which may be unsubstituted or substituted by one or more OH, N(R4)2, COOH or halogen, and (3) when R13 is a terminal group, selected from the group consisting of C1-10alkyl, C1-10alkenyl, C1-10alkynyl, all of which may be linear or branched, or phenyl, all of which may be unsubstituted or substituted by one or more OH, N(R4)2, COOH or halogen, with the proviso that when R7 or R9 is â€”(CH2)pâ€”Xâ€”R13, p is 0 and X is O then R13 is not a linear or branched alkyl chain of 1 to 8 carbon atoms; R14 is hydrogen, C1-6alkyl, C2-6alkenyl or C2-7alkynyl; X is (CH2)p, O, NR4 or S(O)p; Y is CH3 or X(CH2)pAr, with the proviso that when R7 or R9 is Xâ€”R13â€”Y, X is O and R13 is a bond, then Y is not CH3; q is zero, one or two; p is an integer from 0 to 6; m is 1, 2 or 3; n is 1 to 4; x is 0 to 4; y is 1 or 2; the dotted line signifies the optional presence of a bond such that it represents a single or double bond.