Compounds with gastric antisecretory activity. 1. Phenoxyalkylamines.
A series of 0-alkylphenoxyalkylamines, derived from classical H1 antagonists, has been found to inhibit histamine-induced gastric acid secretion. The most potent compound was trans-1-[2[2-[2-(1-adamantyl)vinyl] phenoxy] ethyl]pyrrolidine (54). The 0-acylphenol 23 required for the preparation of 54 was obtained by the novel reaction of 1-bromoadamantane (21) with 4-hydroxycoumarin (20) using diethyl phosphonate as solvent. The product 22 was then hydrolyzed under basic conditions to give 23 in high yield. 54 was not an H2 antagonist and its mode of action remains unknown. The compound had no significant anticholinergic, antiinflammatory, anticonvulsant, sedative, or H1-antihistaminic activity.
D000218:Adamantane / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D000588:Amines / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D003864:Depression, Chemical; D004347:Drug Interactions; D005750:Gastric Juice / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D010647:Phenyl Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000588:Amines; D010647:Phenyl Ethers; D011759:Pyrrolidines; D006632:Histamine; D000218:Adamantane