摘要 |
The invention related to colchinol derivatives of the formula (I): Wherein: R<1>; R<2 >and R<3 >are each independently hydroxy, phosphoryloxy (-OP3H2), C1-4alkoxy or an in vivo hydrolysable ester of hydroxy, with the proviso that at least 2 of R<1>, R<2 >and R<3 >are C1-4alkoxy; A is -CO-, -C(O)O-, -CON(R<8>)- (wherein R<8 >is hydrogen, C1-4alkyl, C1-3alkoxyC1-3alkyl, aminoC1-3alkyl or hydroxyC1-3alkly); a is an integer from 1 to 4 inclusive; R<a >and R<b >are independently selected from hydrogen, hydroxy and amino; B is -O-, -CO-, N(R<9>)CO-, -CON(R<9>)-, -N(R<9>)C(O)O-, -N(R<9>)CON(R<10>)-, -N(R<9>)SO2-, -SO2N(R<9>)- or a direct single blond (wherein R<9 >and R<10 >are independently selected from hydrogen, C1-4alkyl, C1-3alkoxyC1-3alkyl, aminoC1-3alkyl and hydroxyC1-3alkyl); b is O or an integer from 1 to 4 inclusive, (provided that when b is O, B is a single direct bond); D is carboxy, sulpho, tetrazolyl, imidazolyl, phosphoryloxy, hydroxy, amino, N-(C1-4alkyl)amino, N,N-di(C1-3alkyl)amino, or of the formula -Y<1>(CH2)0R<11 >or -NHCH(R<12>)COOH; [wherein Y<1 >is a direct single bond, -O-, -C(O)-, -N(R<13>)C(O)- or -C(O)N(R<13>)- (wherein R<13 >is hydrogen, C1-4alkyl, C1-3alkoxyC2-3alkyl, aminoC2-3alkyl or hydroxyC2-3alkyl); e is O or an integer from 1 to 4 inclusive.
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