Gul Halise Inci, Calis Unsal, Vepsalainen Jouko
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey.
Arzneimittelforschung. 2002;52(12):863-9. doi: 10.1055/s-0031-1299982.
Some acetophenone derived bis Mannich bases (B1-B5) and piperidinols (C1, C4), which are the structural isomers of B1 and B4, and also quaternary piperidine derivative C6 were synthesized and studied for anticonvulsant activity. Of the compounds, C6 was reported for the first time. Chemical structures of the compounds were confirmed by UV, IR, 1H-NMR, 13C-NMR, mass spectra and elemental analysis. Their anticonvulsant activities were determined by maximal electroshock (MES), subcutaneous metrazol (scMet) tests and rotarod test for neurological deficits. According to the activity studies, B2, B4, C1 and C4 derivatives were found to be protective against MES at 30 mg/kg and above. B1, B2, B3, B4, C4 and C6 derivatives were found to be protective against scMet. at different dose levels ranging from 30 to 300 mg/kg. Since no neurotoxicity was detected for the compounds B4 and C4, they seem to be candidate compounds for further synthesis and in vivo studies for their potential anticonvulsant activity.
合成了一些苯乙酮衍生的双曼尼希碱（B1 - B5）和哌啶醇（C1、C4，它们是B1和B4的结构异构体）以及季铵哌啶衍生物C6，并对其抗惊厥活性进行了研究。其中，化合物C6为首次报道。通过紫外光谱、红外光谱、1H - 核磁共振、13C - 核磁共振、质谱和元素分析确定了这些化合物的化学结构。通过最大电休克（MES）、皮下注射戊四氮（scMet）试验以及用于评估神经功能缺损的转棒试验测定了它们的抗惊厥活性。根据活性研究，发现B2、B4、C1和C4衍生物在30 mg/kg及以上剂量时对MES具有保护作用。发现B1、B2、B3、B4、C4和C6衍生物在30至300 mg/kg的不同剂量水平下对scMet具有保护作用。由于未检测到化合物B4和C4具有神经毒性，它们似乎是进一步合成以及进行体内研究以探究其潜在抗惊厥活性的候选化合物。
