Nikolova M, Fajad K, Natova L
Chemical Pharmaceutical Research Institute, Sofia, Bulgaria.
Farmaco. 1993 Apr;48(4):459-72.
Fifteen original piperazine derivatives were synthesized: 11 esters of 1-substituted-4-(3'-phenyl-3'-hydroxypropyl)-piperazines with acetic, propionic, benzoic and phenylacetic acids and 4 symmetrical esters of 1,4-bis-(3'-phenyl-3'-hydroxypropyl)-piperazine with acetic, propionic, benzoic and phenylacetic acids. The compounds were tested with respect to their analgesic and behavioural activity, as well as toxicity. Three nociceptive tests were used: chemical intraperitoneal irritation with acetic acid, thermal contact irritation and thermal radiation irritation. The tests were performed on albino mice breed H. All tested compounds were biologically active and showed analgesic effect. The "therapeutic index" was determined on the basis of the mean effective doses (ED50) and the mean lethal doses (LD50). Most favorable "therapeutical" indices were distinguished in 1,4-bis[3'-phenyl-3'-acetoxypropyl]-piperazine (12), 1-benzhydryl-4[3'-benzyloxypropyl]-piperazine (10) and 1-benzhydryl-4[3'-phenyl-3'-phenylacetyloxypropyl]-piperazine (11).
合成了15种原哌嗪衍生物：11种1-取代-4-(3'-苯基-3'-羟丙基)-哌嗪与乙酸、丙酸、苯甲酸和苯乙酸的酯，以及4种1,4-双-(3'-苯基-3'-羟丙基)-哌嗪与乙酸、丙酸、苯甲酸和苯乙酸的对称酯。对这些化合物进行了镇痛、行为活性以及毒性测试。使用了三种伤害感受测试：乙酸腹腔化学刺激、热接触刺激和热辐射刺激。测试在繁殖的白化小鼠上进行。所有测试化合物均具有生物活性并显示出镇痛作用。根据平均有效剂量（ED50）和平均致死剂量（LD50）确定“治疗指数”。在1,4-双[3'-苯基-3'-乙酰氧基丙基]-哌嗪（12）、1-二苯甲基-4[3'-苄氧基丙基]-哌嗪（10）和1-二苯甲基-4[3'-苯基-3'-苯乙酰氧基丙基]-哌嗪（11）中区分出了最有利的“治疗”指数。
