Syntheses and gastric acid antisecretory properties of the H2-receptor antagonist N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]thieno[3,4-d]isothiazol-3-amine 1,1-dioxide and related derivatives

Abstract

The synthesis and gastric acid antisecretory properties of several N-substituted thieno[3,4-d]isothiazol-3-amine 1,1-dioxides and analogues are described. Two of the more potent compounds, N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]thieno[3,4-d] isothiazol-3-amine 1,1-dioxide (6a) and N-[4-[3-(1-piperidinylmethyl)phenoxy]propyl]thieno[3,4-d] isothiazol-3-amine 1,1-dioxide, showed greater potencies as H2-receptor antagonists (in vitro) than ranitidine. They also had potent gastric acid antisecretory activities in vivo, inhibiting basal acid secretion in the rat, histamine-stimulated acid secretion in the dog, and food-stimulated acid secretion in the dog. These were selected for further pharmacological evaluation.