4-亚氨基恶唑烷-2-酮作为氰醇部分的生物等排体：肠道病毒 71 3C 蛋白酶抑制剂。
4-Iminooxazolidin-2-one as a Bioisostere of the Cyanohydrin Moiety: Inhibitors of Enterovirus 71 3C Protease.
机构信息
College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Molecular Drug Research , Nankai University , Tianjin 300350 , China.
Department of Biochemistry and Biophysics , Texas A&M University , College Station , Texas 77843 , United States.
出版信息
J Med Chem. 2018 Nov 21;61(22):10333-10339. doi: 10.1021/acs.jmedchem.8b01335. Epub 2018 Nov 8.
A recently reported potent inhibitor of enterovirus 71 3C protease, ( R)-1, was found to have stability and potential toxicity issues due to the presence of a cyanohydrin moiety. Modifying the labile cyanohydrin moiety, by serendipity, led to the discovery of 4-iminooxazolidin-2-one-based inhibitors 4e and 4g with potent inhibitory activity and significantly improved stability. In vivo pharmacokinetic studies of 4e also demonstrated high plasma exposure and moderate half-life. These compounds have shown potential of becoming anti-EV71 drug candidates.
一种最近报道的肠道病毒 71 型 3C 蛋白酶的有效抑制剂（R）-1，由于存在氰醇部分，被发现存在稳定性和潜在毒性问题。通过偶然的机会对不稳定的氰醇部分进行修饰，发现了基于 4-亚氨基恶唑烷-2-酮的抑制剂 4e 和 4g，它们具有很强的抑制活性和显著提高的稳定性。4e 的体内药代动力学研究也表明其具有较高的血浆暴露量和中等半衰期。这些化合物具有成为抗 EV71 药物候选物的潜力。
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