Nitrogen Bridgehead Compounds. 18. New Antiallergic 4H-Pyrido[1,2-a]pyrimidin-4-ones. 1

István Hermecz, Tibor Breining, Zoltán Mészáros, Agnes Horváth, Lelle Vasvári-Debreczy, Franz Dessy, Christine DeVos, Ludovic Rodriguez

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33 Citations (Scopus)

Abstract

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 ED50value of 1.0 µmol/kg po and is now under clinical investigation.

Original languageEnglish
Pages (from-to)1140-1145
Number of pages6
JournalJournal of Medicinal Chemistry
Volume25
Issue number10
DOIs
Publication statusPublished - Jan 1 1982

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Hermecz, I., Breining, T., Mészáros, Z., Horváth, A., Vasvári-Debreczy, L., Dessy, F., DeVos, C., & Rodriguez, L. (1982). Nitrogen Bridgehead Compounds. 18. New Antiallergic 4H-Pyrido[1,2-a]pyrimidin-4-ones. 1. Journal of Medicinal Chemistry, 25(10), 1140-1145. https://doi.org/10.1021/jm00352a008