4-(Diphenylmethyl)-1-[(imino)methyl]piperidines as gastric antisecretory agents.
4-(Diphenylmethyl)-1-piperidinemethanimine (1) is a potent oral gastric antisecretory agent in rats but contains a strong anticholinergic component. Since a nonanticholinergic gastric antisecretory drug would be useful in the treatment of peptic ulcer disease, a program was initiated by us to find such an agent based on 1. Compound 1 contains structural elements common to the anticholinergics atropine and homatropine. Studies on the structure-activity relationships of these compounds and their derivatives have revealed certain modifications that diminish or abolish anticholinergic activity. The application of these modifications to the design of analogues of 1 afforded an antisecretory compound, 4-(diphenylmethyl)-1-[(octylimino)methyl]piperidine (3h, fenoctimine), which exhibited no anticholinergic activity. Fenoctimine is undergoing clinical trial as a gastric antisecretory drug.
D000818:Animals; D000897:Anti-Ulcer Agents; D001667:Binding, Competitive; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005746:Gastric Emptying / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D010880:Piperidines; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; C037813:fenoctimine