Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
Bioorg Med Chem. 2012 Jun 1;20(11):3551-64. doi: 10.1016/j.bmc.2012.04.002. Epub 2012 Apr 11.
N-Benzyl 2-acetamido-2-substituted acetamides, where the 2-substituent is a (hetero)aromatic moiety, are potent anticonvulsants. We report the synthesis and whole animal pharmacological evaluation of 16 analogues where the terminal 2-acetyl group was removed to give the corresponding primary amino acid derivatives (PAADs). Conversion to the PAAD structure led to a substantial drop in seizure protection in animal tests, demonstrating the importance of the N-acetyl moiety for anticonvulsant activity. However, several of the PAADs displayed notable pain-attenuating activities in a mouse model.
N-苄基 2-乙酰氨基-2-取代乙酰胺，其中 2-取代基是（杂）芳基部分，是有效的抗惊厥药。我们报告了 16 种类似物的合成和全动物药理学评价，其中末端 2-乙酰基被去除得到相应的伯氨基酸衍生物（PAAD）。转换为 PAAD 结构导致在动物试验中保护癫痫发作的能力显著下降，表明 N-乙酰基部分对抗惊厥活性的重要性。然而，在小鼠模型中，一些 PAAD 显示出显著的镇痛活性。
