Synthesis and anti-filarial activity of 6-(3-aminophenyl)-2,3,5,6-tetrahydroimidazol[2,1-b]thiazole derivatives

Abstract Structure activity studies against filariae are described for a series of derivatives of 6-(3-aminophenyl)-2,3,5,6-tetrahydroimidazo[2,1- b ]thiazole ( 15 derivatives. In an in vivo assay using gerbils implanted with both Acanthocheilonema viteae and Brugia pahangi , the former parasite was shown to be the more sensitive to a range of amides of 15 . None of these compounds, however, had any activity at 5 × 10 −5 mol against the worms in vitro suggesting that they required in vivo activation. This was confirmed when the benzamido derivative ( 6 ) was shown to be rapidly metabolised in gerbils to the parent amine ( 15 ). The latter had potent effects on filariae both in vivo and in vitro but was also found to be toxic to mammals and unsuitable for further development. Unsuccessful attempts to improve upon the therapeutic index of 15 through the synthesis of various novel analogues are described.