Rubat C, Coudert P, Albuisson E, Bastide J, Couquelet J, Tronche P
Groupe de Recherches en Pharmacochimie, Clermont-Ferrand, France.
J Pharm Sci. 1992 Nov;81(11):1084-7. doi: 10.1002/jps.2600811108.
A series of 5-arylidenepyridazin-3-ones substituted in the 2-position by an arylpiperazinoalkyl moiety (2-16) was synthesized and evaluated for analgesic activity. In the phenylbenzoquinone-induced writhing test, Mannich bases 2-14 were the most active compounds (6.1 < or = ED50 < or = 43.0 mg/kg, orally; ED50 is the half-maximal effective dose). Pyridazinones 8 and 9, with a 3-chlorophenylpiperazinomethyl substituent, also exhibited significant anti-inflammatory and antipyretic effects. The activities in the phenylbenzoquinone-induced writhing test were subjected to a Hansch analysis, and a significant correlation with lipophilicity and Hammett's constants was obtained.
合成了一系列在2-位被芳基哌嗪基烷基部分取代的5-亚芳基哒嗪-3-酮（2-16），并对其镇痛活性进行了评估。在苯醌诱发的扭体试验中，曼尼希碱2-14是活性最高的化合物（口服半数有效剂量ED50为6.1≤ED50≤43.0mg/kg；ED50是半数最大有效剂量）。具有3-氯苯基哌嗪甲基取代基的哒嗪酮8和9也表现出显著的抗炎和解热作用。对苯醌诱发扭体试验中的活性进行了Hansch分析，结果表明其与亲脂性和哈米特常数具有显著相关性。
