一系列具有催眠活性的新型1-(2-嘧啶基)哌嗪衍生物的构效关系
Structure-activity relationship in a series of new 1-(2-pyrimidinyl)piperazine derivatives with hypnotic activity.
作者信息
Chilmonczyk Z, Bogdal M, Mazgajska M, Cybulski J, Lewandowska U
机构信息
Pharmaceutical Research Institute, Warszawa, Poland.
出版信息
Pol J Pharmacol. 1996 Jul-Aug;48(4):431-40.
Preparation, biological properties and QSAR of new derivatives of 1-[4-(2-pyrimidinyl)-1-piperazinyl]-1, 3-butandione (11-13, and 15-18) and 3-[4-(2-pirimidinyl)-1-piperazinyl]-3-oxopropanoate (20-22) exhibiting hypnotic activity in mice are reported. The best therapeutic indices (TI = LD50/ED50) 4.7 and 9.4 for po and ip administration, respectively, were found for 1-[4-(2-pyrimidinyl)-1-piperazinyl]-2-n-pentyl-1,3-butandione (15). QSAR studies showed that the biological activity grows initially with an increase in lipophilicity to drop dramatically for log P > 2.5.
报道了1-[4-(2-嘧啶基)-1-哌嗪基]-1,3-丁二酮（11 - 13以及15 - 18）和3-[4-(2-嘧啶基)-1-哌嗪基]-3-氧代丙酸酯（20 - 22）的新衍生物的制备、生物学性质及定量构效关系，这些衍生物在小鼠中表现出催眠活性。对于1-[4-(2-嘧啶基)-1-哌嗪基]-2-正戊基-1,3-丁二酮（15），经口给药和腹腔注射给药时分别发现了最佳治疗指数（TI = LD50/ED50），分别为4.7和9.4。定量构效关系研究表明，生物活性最初随着亲脂性的增加而增强，但当log P > 2.5时会急剧下降。
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