| 摘要 |
The invention provides new macrolides antibiotics of formula I with improved biological properties, wherein R1 is hydrogen, cyano or a residue -Y-X-Q; Y is S, SO, S02, NH, NCH3, CH20, CH2NH, CH2N(CH3) or CO; X is a bond or a linear group with up to 9 atoms consisting of C, N, O and/or S, of which up to 2 atoms can be N, one atom can be O or S, one carbon atom can appear as a CO group, one sulphur atom can appear as an SO2 group and two adjacent C atoms can be present as -CH=CH- or -C=-C-; Q is hydrogen, alkyl, heterocyclyl or aryl, which heterocyclyl and aryl groups maybe further substituted; R2 is hydrogen or fluorine; R3 is methyl, -(CH2)3-R5, -CH2CH=CH-R5 or -CH2=C- R5; R5 is heterocyclyl or aryl, which heterocyclyl and aryl groups may be further substituted; Z is O or NOR 4; R4 is hydrogen, alkyl, heterocyclyl, aryl, heterocyclyl alkyl or aralkyl; indicates a chiral centre which is in the (R) or (S) form, i.e. including diastereomeric mixtures and separate stereomeric forms, and pharmaceutically acceptable acid addition salts or in vivo cleavable esters thereof, provided that not simultaneously R2 is hydrogen, R3 is methyl and Z is O when simultaneously Rl is hydrogen, cyano, -S(L)mR6, -S(O)(L)mR6, or -S(O)2(L)mR6; L represents -(CH2)n- or -(CH2)nZl(CH2)n-; m is 0 or 1; n is 1, 2, 3, or 4; n' is 0, 1, 2, 3, or 4; Zl is O, S or NH; and R6 is hydrogen, alkyl, heterocyclyl or aryl; which heterocyclyl and aryl groups maybe further substituted.
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