Chanh P H, Lasserre B, Kaiser R, Couquelet J, Coudert P, Rubat C
Pharmacologie de la Régulation C.N.R.S., Institut de Physiologie, Toulouse, France.
Prostaglandins Leukot Essent Fatty Acids. 1990 Jun;40(2):143-8. doi: 10.1016/0952-3278(90)90157-g.
Experiments carried out under the conditions adopted showed the strong affinity of aminopyridazine derivatives for the eicosanoids TXA2 and PGI2. But this affinity depended on the chemical structure of the molecule: a small change in the radical grafted onto the pyridazine ring could completely modify the pharmacological activity of the molecule. Consequently it should be possible to control the properties of pyridazine derivatives according to pharmacological needs. Thus: --pyridazin-3-one derivatives were mainly active on TXA2 biosynthesis: 2-aminoalkyl 5-arylidene 6-methyl (4H) pyridazin-3-ones inhibited the TXA2-synthesizing activity of cardiac tissue whereas 3-amino 4,6-diaryl pyridazin-3-ones were specific inhibitors of the TXA2 synthetase in vitro, but these effects were weak. --pyridazine derivatives were devoid of any effect on the TXA2-synthesizing activity of cardiac tissue: they acted on either TXA2 synthetase or PGI2 synthetase according to the radicals grafted onto the pyridazine ring. --none of the compounds under study was active on the PGI2-synthesizing activity of cardiac tissue.
在所采用的条件下进行的实验表明，氨基哒嗪衍生物对类二十烷酸TXA2和PGI2具有很强的亲和力。但这种亲和力取决于分子的化学结构：接枝到哒嗪环上的基团发生微小变化可能会完全改变分子的药理活性。因此，应该有可能根据药理需求来控制哒嗪衍生物的性质。具体如下：
哒嗪-3-酮衍生物主要对TXA2生物合成有活性：2-氨基烷基5-亚芳基6-甲基（4H）哒嗪-3-酮抑制心脏组织的TXA2合成活性，而3-氨基4,6-二芳基哒嗪-3-酮在体外是TXA2合成酶的特异性抑制剂，但这些作用较弱。
哒嗪衍生物对心脏组织的TXA2合成活性没有任何影响：根据接枝到哒嗪环上的基团不同，它们作用于TXA2合成酶或PGI2合成酶。
所研究的化合物均对心脏组织的PGI2合成活性没有活性。
