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.
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.
D000818:Animals; D016275:Atrial Function; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists; D008026:Ligation; D008297:Male; D050198:Phenoxypropanolamines; D011708:Pylorus; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D050198:Phenoxypropanolamines; D013844:Thiazoles; D013876:Thiophenes; D006632:Histamine; D011899:Ranitidine; C056444:N-(4-(3-(1-piperidinylmethyl)phenoxy)propyl)thieno(3,4-d)isothiazol-3-amine 1,1,-dioxide; C051466:Wy 45662