Nitrogen bridgehead compounds. 38. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 3.
The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid (4) on the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of appropriate functional groups into position 9 of the pyridopyrimidine ring. The most active 9-substituted pyridopyrimidinecarboxylic acids contained an oxime, a phenylamino, or a (phenylamino)thioxomethyl group in position 9. The 9-phenylcarboxamido and 9-phenylhydrazono moieties may be regarded as bioisosteric groups in the pyridopyrimidinone series. In the series of 9-(arylamino)dihydropyridopyrimidines, the structure-activity relationship study revealed similar relationships as found for the 9-(arylhydrazono)tetrahydropyridopyrimidines. The biological activity was due to the 6S enantiomers. A monosubstituted arylamino moiety in position 9 was necessary for the intravenous activity. The most active compound, 9-[(3-acetylphenyl)amino]-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H- pyrido[1,2-a]pyrimidine-3-carboxylic acid (40) was three times as active as the reference sodium chromoglycate (DSCG) in the passive cutaneous anaphylaxis (PCA) test.
D000818:Animals; D004353:Drug Evaluation, Preclinical; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship
D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; D011744:Pyrimidinones