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 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.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000201:enzymology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D011464:Epoprostenol / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006736:Horses; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000378:metabolism; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D011724:Pyridazines / Q000494:pharmacology*
D001095:Arachidonic Acids; D011724:Pyridazines; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D003577:Cytochrome P-450 Enzyme System; C054746:3-dimethylamino-5-(3'-trifluoromethyl)-6-methyl(4H)-pyridazine; D011464:Epoprostenol; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase