Colchinol derivatives as vascular damaging agents.

摘要

The invention relates to the use of compounds of formula (I): wherein X is -C(O)-, -C(S)-, -C-NOH, or -CH(R⁷)- wherein R⁷ is hydrogen, hydroxy, C_1-7alkoxy, -OR⁸ or -NR⁸R⁹ (wherein R⁸ is a group -Y¹R¹⁰ (wherein Y¹ is a direct bond, -C(O)-, -C(S)-, -S-, -C(O)O-, -C(O)NR¹¹-, -SO₂- or -SO₂NR¹²- (wherein R¹¹ and R¹², which may be the same or different, each independently represents hydrogen; C_1-3alkyl or C_1-3alkoxyC_2-3alkyl) and R¹⁰ is as defined herein, R⁹ includes hydrogen; R¹¹, R¹² and R¹³ are as defined herein and are preferably methyl; R⁴, R⁵ and R⁶ are as defined herein with the proviso that R⁵ is not hydroxy, alkoxy, substituted alkoxy, -OPO₃H₂, -O-C_1-7alkanoyl or benzyloxy; and salts thereof in the manufacture of a medicament for use in the production of a vascular damaging effect in warm-blooded animals such as humans. The present invention further relates to compounds of the formula (I), pharmaceutical compositions containing them, processes for their preparation and to a method of treatment using the compounds to produce a vascular damaging effect in a warm-blooded animal such as a human. The compounds of formula (I) and the pharmaceutically acceptable salts thereof may be useful in the treatment of a number of disease states including cancer and rheumatoid arthritis.