Nitrogen bridgehead compounds. 18. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 1.
A new type of antiallergic agent, 9-hydrazono-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones, was synthesized and evaluated for inhibitory effects in the rat reagenic passive cutaneous anaphylaxis (PCA) screen. Several racemic 6-methyl derivatives were found to be more potent than disodium chromoglycate intravenously and some were also active orally. Structure-activity relationships are discussed. High stereospecificity was observed in the 6-methyl series between the enantiomers with 6S and 6R absolute configuration, the former being more active. Compound 17, (+)-6(S)-methyl-9-(phenylhydrazono)-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid [Chinoin-1045; UCB L140], has an ED50 value of 1.0 mumol/kg po and is now under clinical investigation.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D011744:Pyrimidinones