SYNTHESIS OF 2,4-DISUBSTITUTED THIAZOLES AND SELENAZOLES AS POTENTIALANTIFILARIAL AND ANTITUMOR AGENTS .2. 2-ARYLAMIDO AND 2-ALKYLAMIDO DERIVATIVES OF 2-AMINO-4-(ISOTHIOCYANATOMETHYL)THIAZOLE AND 2-AMINO-4-(ISOTHIOCYANATOMETHYL)SELENAZOLE

The synthesis of a series of 2-arylamido and 2-alkylamido derivatives of 2-amino-4-(isothio-cyanatomethyl)thiazole and 2-amino-4-(isothiocya natomethyl)selenazo is described. In vitro antiproliferative evaluatio ns were carried out using L1210 cells. The 2-(alkylamido)thiazole deri vatives were moderately antiproliferative, with IC50's of 4-8 mu M. A significant increase in activity was obtained for the arylamido deriva tives, with IC50's of 0.2-1 mu M. The results obtained for the selenaz oles were similar to those for the thiazoles. 2-Benzamido-4-(isothiocy anatomethyl)thiazole (19) was found to be a potent inhibitor of GMP sy nthetase. None of the compounds prepared in this study demonstrated an tifilarial activity.