Synthesis and Analgesic Activity of lsoxazolo[3, 4-d]pyrimidines and Isothiazolo [5, 4-d] pyrimidines

Abstract

New synthetic methods for the preparation of isoxazolo[3, 4-d]pyrimidines and isothiazolo[5, 4-d]pyrimidines and their pharmacological activities were proposed.
6-Chloro-5-formyluracils [1] were treated with 2 equivalents of hydroxylamine to give the isoxazolo[3, 4-d]pyrimidines [6a∼f]. Compound [6a] was also synthesized by reaction of the oxime of [1] with an equivalent of hydroxylamine or by the Vilsmeier reaction of 6- (hydroxyamino)uracil [5]. The 3-substituted derivatives [4] and [6g∼j] were prepared by treatment of 6-chloro-5-cyanouracil [3] with hydroxylamine or by heating [5] in acid anhydrides. Isothiazolo[5, 4-d]pyrimidine. [11] was synthesized conveniently by the Vilsmeier reaction of 6-mercaptouracil [8] followed by the treatment with hydroxylamine. Compound [11] wa s also prepared by heating the oxime [2] with sodium hydrogensulfide. Some resulting compounds [6a, 6b, 6i, 11] showed an analgesic activity. Especially, [6 a] and [11] were about 6 times more active than aminopyrine.