Nitrogen bridgehead compounds. Part 18. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. Part I
作者:Istvan Hermecz、Tibor Breining、Zoltan Meszaros、Agnes Horvath、Lelle Vasvari-Debreczy、Franz Dessy、Christine DeVos、Ludovic Rodriquez
DOI:10.1021/jm00352a008
日期:1982.10
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
合成了一种新型的抗过敏药9-肼基-6,7,8,9-四氢-4H-吡啶并[1,2-a]嘧啶-4-酮,并评估了其对大鼠自发性被动皮肤的抑制作用。过敏反应(PCA)屏幕。已发现几种消旋的6-甲基衍生物在静脉内比色甘氨酸二钠更有效,有些还具有口服活性。讨论了构效关系。在具有6S和6R绝对构型的对映异构体之间的6-甲基系列中观察到高立体特异性,前者更具活性。化合物17,(+)-6(S)-甲基-9-(苯肼基)-4-氧代-4H-吡啶并[1,2-a]嘧啶-3-羧酸[Chinoin-1045; [UCB L140],ED50值为1.0 mumol / kg po,目前正在临床研究中。