title: Nitrogen bridgehead compounds. 44. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 4.
abstract: The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carbox yli c acid (1) in the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of an (arylamino)methylene moiety into position 9 of the pyridopyrimidine ring. Compound 34, (+)-6(S)-methyl-9-[(m-methylphenyl)-hydrazono]-4-oxo-4H-pyrido[1,2 -a] pyrimidine-3-carboxylic acid, displayed about 10 000 times the activity of the starting compound 1. A structure-activity relationship study of 9-[(arylamino)methylene]tetrahydropyridopyrimidine-3-carb ox ylic acids resulted in conclusions similar to those found for the 9-(arylhydrazono)tetrahydro-and 9-(arylamino)dihydropyridopyrimidine series. Replacement of the 3-carboxy group of 9-(phenylhydrazono)-tetrahydropyridopyrimidin-4-ones with an acrylic acid moiety caused slight increases in potency. In the 6-methyl-substituted series, a high stereospecificity was observed between the enantiomers with 6S and 6R absolute configurations, the former being responsible for the antiallergic activity. The effects of some 9-[(arylamino)-methylene]tetrahydropyridopyrimidine-3-car box ylic acids on the rat passive peritoneal anaphylaxis test were also investigated.
mesh_terms: D000707:Anaphylaxis; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009904:Optical Rotation; D010323:Passive Cutaneous Anaphylaxis; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; D011744:Pyrimidinones