Colchinol derivatives as vascular damaging agents

Abstract

The invention relates to the use of compounds of formula (I): wherein X is —C(O)—, —C(S)—, —C═NOH, or —CH(R)— wherein Ris hydrogen, hydroxy, Calkoxy, —ORor —NRR(wherein Ris a group —YR(wherein Yis a direct bond, —C(O)—, —C(S)—, —S—, —C(O)O, —C(O)NR—, —SO— or —SONR— (wherein Rand R, which may be the same or different, each independently represents hydrogen, Calkyl or CalkoxyCalkyl) and Ris as defined herein, and Rincludes hydrogen; R, Rand Rare as defined herein and are preferably methyl; R, Rand Rare as defined herein with the proviso that Ris not hydroxy, alkoxy, substituted alkoxy, —OPOH, —O—Calkanoyl 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.