Uysal S, Calis U, Soyer Z
Department of Pharmaceutical Chemistry, Ege University, Bornova, Izmir, Turkey.
Arzneimittelforschung. 2012 Jun;62(6):295-300. doi: 10.1055/s-0032-1308982. Epub 2012 Apr 2.
In this study, the synthesis and anticonvulsant properties of sixteen 2/3-benzoylaminopropionanilide derivatives were described. Molecular design of the compounds has been based on the modification of lacosamide which is a functionalized amino acid with a novel anticonvulsant activity. The structural confirmation of the title compounds was achieved by spectral and analytical data. The anticonvulsant activity profile of synthesized compounds was determined by maximal electroshock (MES) and subcutaneous metrazole (scMet) seizure tests, whereas their neurotoxicity was examined using rotarod test. All these tests were performed in accordance with the procedures of the Antiepileptic Drug Development (ADD) program. The majority of the compounds were effective in the MES or scMet screening tests. None of the compounds showed neurotoxicity according to the rotarod test at studied doses. Most active compounds in the series were 3, 12 and 13, which bearing 2-methyl, 2-ethyl and 2-isopropyl substituent on the N-phenyl ring, respectively.
本研究描述了十六种2/3-苯甲酰基氨基丙酰苯胺衍生物的合成及其抗惊厥特性。这些化合物的分子设计基于对拉科酰胺的修饰，拉科酰胺是一种具有新型抗惊厥活性的官能化氨基酸。通过光谱和分析数据对标题化合物进行了结构确证。通过最大电休克（MES）和皮下注射戊四氮（scMet）惊厥试验测定合成化合物的抗惊厥活性谱，而使用转棒试验检测其神经毒性。所有这些试验均按照抗癫痫药物开发（ADD）计划的程序进行。大多数化合物在MES或scMet筛选试验中有效。在所研究的剂量下，根据转棒试验，没有一种化合物显示出神经毒性。该系列中活性最高的化合物是3、12和13，它们在N-苯环上分别带有2-甲基、2-乙基和2-异丙基取代基。
