Isothiazoles. Part XV. A mild and efficient synthesis of new antiproliferative 5-sulfanylsubstituted 3-alkylaminoisothiazole 1,1-dioxides

5-Sulfanyl-3-alkylaminoisothiazole dioxide derivs. have been identified as a new class of potent inhibitors of rat aortic myocite proliferation. They were prepd. by applying a simple methodol. able to introduce a heteroatom on C-5 of the 3-alkylaminoisothiazole dioxide system. 3-Amino-substituted-5-chloroisothiazole dioxides react smoothly not only with S-nucleophiles but also with N- and O-nucleophiles affording the corresponding 5-heterosubstituted isothiazole dioxides through an addn.-elimination reaction. The behavior of 3-alkylamino-4-bromoisothiazole 1,1-dioxide with S-, N- and O-nucleophiles affording the same products has also been described. On the contrary, the 3-amino-4,5-unsubstituted isothiazole dioxide system reacts easily only with sulfur nucleophiles affording the corresponding 4,5-dihydro-5-sulfanyl derivs. through a simple Michael addn. reaction