Xu P, Wang S Y, Chen Y, Liu W Q, Tao C
Department of Medicinal Chemistry, Beijing Medical University.
Yao Xue Xue Bao. 1991;26(9):656-60.
In searching for effective anticonvulsant agent fourteen 6-(substituted-phenyl)-4,5-dihydro-3 (2H) pyridazinones and fifteen 6-(substitutedphenyl)-3 (2H) pyridazinones have been synthesized and screened in mice for their ability to antagonize maximal electroshock seizure (MES). The ED50 values showed that 6-(2',4'-dichlorophenyl)-3 (2H) pyridazinone was the most potent anticonvulsant in these compounds. The structure--activity relationships in these two series were examined. We came to the conclusion that the higher is the hydrophobic parameter pi of the substituent on phenyl ring, the more potent anticonvulsant is the compound. And also, only the compounds with an electronwithdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.
在寻找有效的抗惊厥药物的过程中，已经合成了14种6 -（取代苯基）-4,5 - 二氢-3（2H）哒嗪酮和15种6 -（取代苯基）-3（2H）哒嗪酮，并在小鼠中筛选它们对抗最大电休克惊厥（MES）的能力。半数有效剂量（ED50）值表明，6 -（2'，4'-二氯苯基）-3（2H）哒嗪酮是这些化合物中最有效的抗惊厥药物。研究了这两个系列的构效关系。我们得出的结论是，苯环上取代基的疏水参数π值越高，该化合物的抗惊厥活性就越强。而且，只有苯环上带有吸电子取代基的化合物才表现出明显的抗惊厥活性。
