4-(Diphenylmethyl)-1-(iminomethyl)piperidines as gastric antisecretory agents

• Published in: Journal of medicinal chemistry Vol. 26; no. 4; pp. 535 - 538
• Main Authors: Scott, Malcolm K, Jacoby, Henry I, Mills, John E, Bonfilio, Antoinette C, Rasmussen, C. Royce
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.04.1983
• Subjects: Animals; Anti-Ulcer Agents; Binding, Competitive; Carbachol - pharmacology; Female; Gastric Acid - metabolism; Gastric Emptying - drug effects; Piperidines - pharmacology; Quinuclidinyl Benzilate - metabolism; Rats; Receptors, Muscarinic - metabolism; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00358a014

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.