B-973，一种新型α7烟碱乙酰胆碱受体激动剂-正向变构调节剂：外消旋体和不对称合成、电生理研究及评估
B-973, a Novel α7 nAChR Ago-PAM: Racemic and Asymmetric Synthesis, Electrophysiological Studies, and Evaluation.
作者信息
Garai Sumanta, Raja Krishnamohan S, Papke Roger L, Deschamps Jeffrey R, Damaj M Imad, Thakur Ganesh A
机构信息
Department of Pharmaceutical Sciences, Bouvé College of Health Science, Northeastern University, 140 The Fenway, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32611, United States.
出版信息
ACS Med Chem Lett. 2018 Oct 11;9(11):1144-1148. doi: 10.1021/acsmedchemlett.8b00407. eCollection 2018 Nov 8.
Abstract
We report here the total synthesis of B-973 (five steps), a recently identified α7 nAChR ago-PAM, its enantiomeric resolution, and its electrophysiological characterization in oocytes to identify (-)-B-973B as the bioactive enantiomer. The asymmetric synthesis of B-973B was accomplished in 99% ee, and X-ray crystallography studies revealed its absolute "" stereochemistry. B-973B was effective in attenuating pain behavior and decreasing paw edema (formalin test), and its analgesic effects were mediated through α7 nAChR.
摘要
我们在此报告了B-973（五步反应）的全合成，它是最近鉴定出的一种α7烟碱型乙酰胆碱受体前体正变构调节剂，对其进行了对映体拆分，并在卵母细胞中进行了电生理特性研究，以确定(-)-B-973B为生物活性对映体。B-973B的不对称合成以99%的对映体过量完成，X射线晶体学研究揭示了其绝对立体化学结构。B-973B在减轻疼痛行为和减轻爪部水肿（福尔马林试验）方面有效，其镇痛作用是通过α7烟碱型乙酰胆碱受体介导的。
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