新型3-苯基-和3,3-二苯基-琥珀酰亚胺的N-吡啶基衍生物的合成、理化性质及抗惊厥特性

Synthesis, physicochemical and anticonvulsant properties of new N-pyridyl derivatives of 3-phenyl- and 3,3-diphenyl-succinimides.

作者信息

Obniska J, Zejc A, Karolak-Wojciechowska J

机构信息

Department of Medicinal Chemistry, Collegium Medicum of Jagiellonian University, Krakow, Poland.

出版信息

Farmaco. 1999 Jul 30;54(7):423-9. doi: 10.1016/s0014-827x(99)00033-6.

DOI:10.1016/s0014-827x(99)00033-6

PMID:10486909

Abstract

Synthesis and physicochemical properties of new N-pyridyl derivatives of 3-phenyl and 3,3-diphenylsuccinimides (1-12) have been described. The obtained compounds were evaluated in respect of their anticonvulsant activity. The N-pyridyl derivatives of 3-phenylsuccinimides (7-12) abolished the protection against MES- and scMET-induced seizures, whereas N-pyridyl derivatives of 3,3-diphenylsuccinimides (1-6) were inactive. After molecular modelling and quantum-chemistry calculations the theoretical activity test was applied (W. Kwiatkowski, J. Karolak-Wojciechowska, SAR and QSAR Envir. Res. 1 (1993) 233; Chem. Abstr. 120, 153001 (1994). J. Karolak-Wojciechowska, M. Blaszczyk, W. Kwiatkowski, J. Obniska, A. Zejc, J. Chem. Cryst. 27 (1997) 297; Chem. Abstr. 127, 277834k (1997)). The molecular electrostatic potential (MEP) of the active compounds differed significantly from that of the inactive ones.

摘要

已描述了3-苯基和3,3-二苯基琥珀酰亚胺的新型N-吡啶基衍生物（1-12）的合成及其物理化学性质。对所得化合物的抗惊厥活性进行了评估。3-苯基琥珀酰亚胺的N-吡啶基衍生物（7-12）消除了对最大电休克（MES）和皮下甲硫氨酸（scMET）诱导的癫痫发作的保护作用，而3,3-二苯基琥珀酰亚胺的N-吡啶基衍生物（1-6）则无活性。在进行分子建模和量子化学计算后，应用了理论活性测试（W. Kwiatkowski，J. Karolak-Wojciechowska，《SAR和QSAR环境研究》1（1993）233；《化学文摘》120，153001（1994）。J. Karolak-Wojciechowska，M. Blaszczyk，W. Kwiatkowski，J. Obniska，A. Zejc，《化学晶体学杂志》27（1997）297；《化学文摘》127，277834k（1997））。活性化合物的分子静电势（MEP）与非活性化合物的分子静电势有显著差异。