GF 抑制的人乙酰胆碱酯酶新型非季铵盐复活剂的设计、合成与表征
Design, synthesis, and characterization of novel, nonquaternary reactivators of GF-inhibited human acetylcholinesterase.
作者信息
McHardy Stanton F, Bohmann Jonathan A, Corbett Michael R, Campos Bismarck, Tidwell Michael W, Thompson Paul Marty, Bemben Chris J, Menchaca Tony A, Reeves Tony E, Cantrell William R, Bauta William E, Lopez Ambrosio, Maxwell Donald M, Brecht Karen M, Sweeney Richard E, McDonough John
机构信息
Southwest Research Institute, Chemistry and Chemical Engineering Division, Department of Medicinal and Process Chemistry, 6220 Culebra Road, San Antonio, TX 78266, USA.
Southwest Research Institute, Chemistry and Chemical Engineering Division, Department of Medicinal and Process Chemistry, 6220 Culebra Road, San Antonio, TX 78266, USA.
出版信息
Bioorg Med Chem Lett. 2014 Apr 1;24(7):1711-4. doi: 10.1016/j.bmcl.2014.02.049. Epub 2014 Feb 28.
The goal of this research was to identify structurally novel, non-quaternarypyridinium reactivators of GF (cyclosarin)-inhibited hAChE that possess the capacity to mediate in vitro reactivation of GF-inhibited human acetylcholinesterase (hAChE). New compounds were designed, synthesized and assessed in GF-inhibited hAChE assays. Structure activity relationships for AChE binding and reactivation of GF-inhibited hAChE were developed. Lead compounds from two different chemical series, represented by compounds 17 and 38, displayed proficient in vitro reactivation of GF-inhibited hAChE, while also possessing low inhibition of native enzyme.
本研究的目标是鉴定出结构新颖的、非季铵吡啶类的GF（环沙林）抑制的人乙酰胆碱酯酶（hAChE）的重活化剂，这些重活化剂具有介导体外重活化GF抑制的人乙酰胆碱酯酶（hAChE）的能力。设计、合成了新化合物，并在GF抑制的hAChE测定中进行了评估。建立了AChE与GF抑制的hAChE结合及重活化的构效关系。由化合物17和38代表的两个不同化学系列的先导化合物，在体外能有效重活化GF抑制的hAChE，同时对天然酶的抑制作用也较低。
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