Monge A, Parrado P, Font M, Fernández-Alvarez E
J Med Chem. 1987 Jun;30(6):1029-35. doi: 10.1021/jm00389a012.
A series of new derivatives of 4-hydrazino-5H-pyridazino[4,5-b]indole (5) and 4-hydrazinopyridazino[4,5-a]indole (12) have been synthesized to investigate their activities as selective thromboxane synthetase inhibitors as well as antihypertensive agents. Several of the prepared compounds were found to be selective thromboxane synthetase inhibitors, in concordance with the Gorman model. The most potent were 8-(benzyloxy)-3,4-dihydro-4-oxo-5H-pyridazino[4,5-b]indole (3c) and 8-methoxy-4-hydrazino-5H-pyridazino[4,5-b]indole (5). This last compound did not inhibit prostacyclin formation and showed an antihypertensive activity similar to that of hydralazine. The acute toxicity in mice for 5a . HCl is about 2.2 times less than that for hydralazine.
合成了一系列4-肼基-5H-哒嗪并[4,5-b]吲哚（5）和4-肼基哒嗪并[4,5-a]吲哚（12）的新衍生物，以研究它们作为选择性血栓素合成酶抑制剂以及抗高血压药物的活性。根据戈尔曼模型，发现所制备的几种化合物是选择性血栓素合成酶抑制剂。最有效的是8-（苄氧基）-3,4-二氢-4-氧代-5H-哒嗪并[4,5-b]吲哚（3c）和8-甲氧基-4-肼基-5H-哒嗪并[4,5-b]吲哚（5）。后一种化合物不抑制前列环素的形成，并且显示出与肼屈嗪相似的抗高血压活性。5a·HCl对小鼠的急性毒性比肼屈嗪低约2.2倍。
