42-RAPAMYCIN HYDROXYESTER, PROCESS FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING IT

摘要

A compound of structure (I) wherein R<1> and R<2> are each, independently, hydrogen or -CO(CR<3>R<4>)b(CR<5>R<6>)dCR<7>R<8>R<9> ; R<3> and R<4> are each, independently, hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, or -F; R<5> and R<6> are each, independently, hydrogen, alkyl, alkenyl, alkynyl, -(CR<3>R<4>)fOR<10>, -CF3, -F, or -CO2R<11>, or R<5> and R<6> may be taken together to form X or a cycloalkyl ring that is optionally mono-, di-, or tri-substituted with -(CR<3>R<4>)fOR<10>; R<7> is hydrogen, alkyl, alkenyl, alkynyl, -(CR<3>R<4>)fOR<10>, -CF3, -F, or -CO2R<11>; R<8> and R<9> are each, independently, hydrogen, alkyl, alkenyl, alkynyl, -(CR<3>R<4>)fOR<10>, -CF3, -F, or -CO2R<11>, or R<8> and R<9> may be taken together to form X or a cycloalkyl ring that is optionally mono-, di-, or tri-substituted with -(CR<3>R<4>)fOR<10>; R<10> is hydrogen, alkyl, alkenyl, alkynyl, tri-(alkyl)silyl, tri-(alkyl)silylethyl, triphenylmethyl, benzyl, alkoxymethyl, tri-(alkyl)silylethoxymethyl, chloroethyl, or tetrahydropyranyl; R<11> is hydrogen, alkyl, alkenyl, alkynyl, or phenylalkyl; X is 5-(2,2-dialkyl)Ä1,3Üdioxanyl, 5-(2,2-dicycloalkyl)Ä1,3Üdioxanyl, 4-(2,2-dialkyl)Ä1,3Ü-dioxanyl, 4-(2,2-dicycloalkyl)Ä1,3Üdioxanyl, 4-(2,2-dialkyl)Ä1,3Üdioxalanyl, or 4-(2,2-dicycloalkyl)Ä1,3Üdioxalanyl; b = 0-6; d = 0-6; and f = 0-6 with the proviso that R<1> and R<2> are both not hydrogen and further provided that either R<1> or R<2> contains at least one -(CR<3>R<4>)fOR<10>, X, or -(CR<3>R<4>)fOR<10> substituted cycloalkyl group, or a pharmaceutically acceptable salt thereof which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.