A Novel Class of Antiulcer Agents. 4-Phenyl-2-(1-piperazinyl)quinolines

• Published in: Chemical & pharmaceutical bulletin Vol. 37; no. 1; pp. 110 - 115
• Main Authors: HINO, Katsuhiko, KAWASHIMA, Katsuyoshi, OKA, Makoto, NAGAI, Yasutaka, UNO, Hitoshi, MATSUMOTO, Jun-ichi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.01.1989; Maruzen; Japan Science and Technology Agency
• Subjects: 2-(4-ehtly-1-piperazinyl)-4-phenylquinoline dimeleate; Animals; Anti-Ulcer Agents - chemical synthesis; Chemical Phenomena; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Male; Mice; Organic chemistry; Preparations and properties; Quinolines - chemical synthesis; Quinolines - pharmacology; Rats; Rats, Inbred Strains
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.37.110

The synthesis of a novel class of antiulcer agents, the substituted 4-phenyl-2-(1-piperazinyl)quinolines, and their pharmacological activities (inhibitory effects on hypothermia induced by reserpine and on gastric ulcers induced by stress or ethanol) are described. These compounds can be classified into three groups (a group predominantly effective on the stress-induced ulcer, one effective on both the stress- and ethanol-induced ulcers, and one selectively effective on the ethanol-induced ulcer), with regard to antiulcer activity. The inhibitory effect on stress-induced ulcer was found to be in close relation to the antagonism of hypothermia. The structure-activity relationships in these compounds are described. Among the compounds, 2-(4-ethyl-1-piperazinyl)-4-phenylquinoline dimaleate (9, AS-2646) showed a potent inhibition of stress-induced ulcer and gastric acid secretion, possively through action on the central nervous system, and it was selected for clinical evaluation.