6-thienyl and 6-phenylimidazo[2,1-b]thiazoles as inhibitors of mitochondrial NADH dehydrogenase

Starting from the potent inhibitory effect of the previously described 2 me thyl-6-(2-thienyl)imidazo[2,1-b]thiazol on mitochondrial complex I, we prep ared a series of derivatives in order to study the effect of a different su bstitution at the positions 2, 5 and 6. The replacement of the thienyl grou p at position 6 with a phenyl group does not modify the biological behaviou r of the lead compound, whereas the shift of the methyl group from position 2 to position 5 yields a compound devoid of inhibitory effects. In both th e 6-thienyl and 6-phenyl series, the lengthening of the chain at position 2 has provided useful information to outline the structural determinants of the ubiquinone antagonist action in imidazothiazole derivatives. (C) 1999 E ditions scientifiques et medicales Elsevier SAS.