Synthesis and biological evaluation of 2-and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization

Two new series of inhibitors of tubulin polymn. based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene mol. skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymn., and cell cycle effects. Although many more 3-amino derivs. have been synthesized so far, the most promising compd. in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concns. and interacts strongly with tubulin by binding to the colchicine site.