一种从氨基吡啶衍生的前列环素生物合成抑制剂

Pham Huu Chanh , B. Lasserre , V. Dossou-Gbete , J. Couquelet , P. Tronche
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引用次数: 3

摘要

以马主动脉微粒体为酶源,花生四烯酸为底物,研究了3-二甲氨基5-(3 '三氟甲基苄基苄基)6-甲基(4H)吡啶嗪(PC88)对PGI2生物合成的影响。在所采用的实验条件下,PC88对PGI2的生物合成具有剂量依赖性(ID50 = 6.9×10−4 M±1.87 ×10−7 M),这种抑制作用是复杂的,既不是竞争性的,也不是非竞争性的。3-二甲氨基5-(2′,6′-二氯苄基6-甲基-(4H)-吡嗪(PC89)促进了PGI2的生物合成。值得注意的是,苯酚环上1和4号碳原子上的2cl被2号碳原子上的CF3取代。这似乎逆转了分子对PGI2合成的活性。PC88和PC89均为TXA2合成酶抑制剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An inhibitor of prostacyclin biosynthesis derived from aminopyridazine

The effects of 3-dimethylamino 5-(3′ trifluoromethylbenzylidene) 6-methyl (4H)-pyridazine (PC88) on the biosynthesis of PGI2, using horse aorta microsomes as a source of enzyme and arachidonic acid as a substrate, were investigated. Under the experimental conditions adopted, PC88 was shown to dosedependently inhibit PGI2 biosynthesis (ID50 = 6.9×10−4 M ± 1.87 × 10−7 M). This inhbitory effect of PC88 was complex: it was of neither competitive nor non-competitive type. 3-dimethylamino 5-(2′,6′-dichlorobenzylidene 6-methyl-(4H)-pyridazine (PC89) enhanced the biosynthesis of PGI2. It is worth noticing the replacement of the 2 Cl at carbon atoms 1 and 4 by a CF3 at carbon atom 2 of the phenol ring. This appears to reverse the activity of the molecule on the synthesis of PGI2. PC88 and PC89 were both inhibitors of TXA2 synthetase.

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