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

J Med Chem. 1988 Jul;31(7):1480-6. doi: 10.1021/jm00402a039.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Atrial Function
  • Chemical Phenomena
  • Chemistry
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Gastric Acid / metabolism*
  • Gastric Mucosa / drug effects
  • Guinea Pigs
  • Heart Atria / drug effects
  • Heart Rate / drug effects
  • Histamine / pharmacology
  • Histamine H2 Antagonists*
  • Ligation
  • Male
  • Phenoxypropanolamines
  • Pylorus
  • Ranitidine / pharmacology
  • Rats
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / pharmacology*
  • Thiophenes / chemical synthesis
  • Thiophenes / pharmacology*

Substances

  • Histamine H2 Antagonists
  • Phenoxypropanolamines
  • Thiazoles
  • Thiophenes
  • Histamine
  • Ranitidine
  • N-(4-(3-(1-piperidinylmethyl)phenoxy)propyl)thieno(3,4-d)isothiazol-3-amine 1,1,-dioxide
  • Wy 45662