Antihypertensives. 1. Syntheses of Thiazino-, Thiazepino-, and Thiazoninoethylguanidines

The discovery of guanethidine¹ has generated considerable interest in compounds which exert their antihypertensive effects by blockade of the adrenergic neurone. Subsequent structure-activity studies have demonstrated that the azocino ring of guanethidine can be altered without loss of antihypertensive activity.² The results of modification of the heterocyclic ring by incorporation of a sulfur atom are described in this paper. Two approaches were selected-insertion of the sulfur atom directly into the ring, guanidines 1 and 2, and bridging of the ring with a sulfur atom, guanidine 3.