一种源自氨基哒嗪的前列环素生物合成抑制剂。
An inhibitor of prostacyclin biosynthesis derived from aminopyridazine.
作者信息
Chanh P H, Lasserre B, Dossou-Gbete V, Couquelet J, Tronche P
机构信息
C.N.R.S. Institut de Physiologie, Toulouse, France.
出版信息
Prostaglandins Leukot Med. 1987 Nov;30(1):1-7. doi: 10.1016/0262-1746(87)90019-9.
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 dose-dependently inhibit PGI2 biosynthesis (ID50 = 6.9 x 10(-4) M +/- 1.87 x 10(-7) M). This inhibitory 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.
以马主动脉微粒体作为酶源、花生四烯酸作为底物，研究了3-二甲基氨基5-（3'-三氟甲基亚苄基）6-甲基（4H）哒嗪（PC88）对前列环素（PGI2）生物合成的影响。在所采用的实验条件下，PC88呈剂量依赖性抑制PGI2生物合成（半数抑制浓度ID50 = 6.9×10⁻⁴M±1.87×10⁻⁷M）。PC88的这种抑制作用很复杂：既不是竞争性类型也不是非竞争性类型。3-二甲基氨基5-（2'，6'-二氯亚苄基）6-甲基（4H）哒嗪（PC89）增强了PGI2的生物合成。值得注意的是，酚环碳原子2上的三氟甲基取代了碳原子1和4上的两个氯原子。这似乎使该分子对PGI2合成的活性发生了逆转。PC88和PC89都是血栓素A2（TXA2）合成酶的抑制剂。
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