Colchinol derivatives functioning as angiogenesis inhibitors, process of their preparation and pharmaceutical composition in which the derivatives are comprised

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 (-OPO3H2), 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 hydroxyC1-3alkyl); a is an integer from 1 to 4 inclusive; R and R 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 bis 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.