Colchinol derivatives as angiogenesis inhibitors

Abstract

The invention related to colchinol derivatives of the formula (I): Wherein: R; Rand Rare each independently hydroxy, phosphoryloxy (—OPH), Calkoxy or an in vivo hydrolysable ester of hydroxy, with the proviso that at least 2 of R, Rand Rare Calkoxy; A is —CO—, —C(O)O—, —CON(R)— (wherein Ris hydrogen, Calkyl, CalkoxyCalkyl, aminoCalkyl or hydroxyCalkly); a is an integer from 1 to 4 inclusive; Rand Rare independently selected from hydrogen, hydroxy and amino; B is —O—, —CO—, N(R)CO—, —CON(R)—, —N(R)C(O)O—, —N(R)CON(R)—, —N(R)SO—, —SON(R)— or a direct single blond (wherein Rand Rare independently selected from hydrogen, Calkyl, CalkoxyCalkyl, aminoCalkyl and hydroxyCalkyl); 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-(Calkyl)amino, N,N-di(Calkyl)amino, or of the formula —Y(CH)Ror —NHCH(R)COOH; [wherein Yis a direct single bond, —O—, —C(O)—, —N(R)C(O)— or —C(O)N(R)— (wherein Ris hydrogen, Calkyl, CalkoxyCalkyl, aminoCalkyl or hydroxyCalkyl); e is O or an integer from 1 to 4 inclusive.