Cignarella G, Barlocco D, Pinna G A, Loriga M, Tofanetti O, Germini M, Sala F
J Med Chem. 1986 Nov;29(11):2191-4. doi: 10.1021/jm00161a010.
A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the previously described 7-cyano derivative, which displayed only antiinflammatory action, the new series exhibited significant antihypertensive and antithrombotic properties. In this respect, the 7-amino (2b) and the 7-acetylamino (2c) derivatives were found to be the most potent and long lasting in reducing the blood pressure in spontaneously hypertensive rats and in protecting mice from the induction of thrombosis. These compounds, as well as the 7-(2-chloropropionyl) derivative 2d, also exhibited antiinflammatory activity; in addition, 2c,d were highly effective in inhibiting indomethacin-induced ulcers in the rat.
已合成了多种7-氨基和7-酰氨基取代的4,4a-二氢-5H-茚并[1,2-c]哒嗪-3-酮，作为降压药6-芳基-5-甲基-4,5-二氢-3(2H)-哒嗪酮的刚性类似物，并作为抗高血压、抗血栓形成、抗溃疡和抗炎剂进行了测试。与之前描述的仅显示抗炎作用的7-氰基衍生物不同，新系列表现出显著的抗高血压和抗血栓形成特性。在这方面，发现7-氨基（2b）和7-乙酰氨基（2c）衍生物在降低自发性高血压大鼠血压和保护小鼠免受血栓形成诱导方面最为有效且作用持久。这些化合物以及7-(2-氯丙酰基)衍生物2d也表现出抗炎活性；此外，2c、d在抑制大鼠吲哚美辛诱导的溃疡方面非常有效。
