Comparative effects of some 3-amino 4,6-diarylpyridazines on the biosynthesis in vitro of TXA 2 and PGI 2- and on the TXA 2- and PGI 2-synthesizing activities of cardiac tissue

• Published in: Prostaglandins, leukotrienes and essential fatty acids Vol. 39; no. 1; pp. 19 - 25
• Main Authors: Pham Huu Chanh, Dossou-Gbete, V., Kaiser, R., Lasserre, B., Chahine, R., Couquelet, J., Coudert, P., Rubat, C.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 1990
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/0952-3278(90)90166-I

Some 3-amino 4,6-diarylpyridazine derivatives were tested for their effects on TXA 2 and PGI 2 biosyntheses in vitro and on the TXA 2- and PGI 2-synthesizing activities of cardiac tissue. Horse platelet and aorta microsomes were used as sources of thromboxane and prostacyclin synthetases respectively. The TXA 2- and PGI 2-synthesizing activities of cardiac tissue were studied on isolated perfused rabbit hearts (the heart microsomes being used both as TXA 2 synthetase and PGI 2 synthetase sources). TXB 2 and 6-keto PGF 1α were determined by RIA. Among the compounds under study, 3-morpholino 4,6-diphenylpyridazine ( III) was shown to inhibit specifically the TXA 2 synthetase. Substitution of the morpholino group by a dimethylamino one ( I) reinforced the inhibiting effects on TXA 2 synthetase but it also revealed a slight anti-prostacyclin synthetase action of the molecule. Replacement of 3-morpholino moieties by either a 3-hydrazino ( IV), or a 2-dimethylaminoethylamino ( V), or a 2-morpholinoethylamino group ( VI) abolished completely the effects of the molecule on TXA 2 and PGI 2 synthetases. Likewise the addition of chlorine on the para-position on the phenyl ring of I neutralized all its inhibitory effects both on TXA 2 and PGI 2 synthetases in vitro. None of the 3-amino 4,6-diarylpyridazine derivatives was active on either the TXA 2- or PGI 2-synthesizing activities of cardiac tissue.