Cbz-Cha-Ala(2-oxopyrrolidin-3-yl)(2-oxopyrrolidin-3-yl)-ol | 1416992-27-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Cbz-Cha-Ala(2-oxopyrrolidin-3-yl)(2-oxopyrrolidin-3-yl)-ol
• 英文别名: benzyl N-[(2S)-3-cyclohexyl-1-[[(2S)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propan-2-yl]amino]-1-oxopropan-2-yl]carbamate
• CAS: 1416992-27-2
• 化学式: C₂₄H₃₅N₃O₅
• 分子量: 445.559
• InChiKey: RFFOSYNGJNIGEB-AKQSQHNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Cbz-Cha-Ala(2-oxopyrrolidin-3-yl)(2-oxopyrrolidin-3-yl)-ol 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 benzyl ((S)-3-cyclohexyl-1-oxo-1-(((S)-1-oxo-3-(2-oxopyrrolidin-3-yl)propan-2-yl)amino)propan-2-yl)carbamate
  参考文献：
  名称：

  Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors

  摘要：

  Noroviruses are the most common cause of acute viral gastroenteritis, accounting for >21 million cases annually in the US alone. Norovirus infections constitute an important health problem for which there are no specific antiviral therapeutics or vaccines. In this study, a series of bisulfite adducts derived from representative transition state inhibitors (dipeptidyl aldehydes and alpha-ketoamides) was synthesized and shown to exhibit anti-norovirus activity in a cell-based replicon system. The ED50 of the most effective inhibitor was 60 nM. This study demonstrates for the first time the utilization of bisulfite adducts of transition state inhibitors in the inhibition of norovirus 3C-like protease in vitro and in a cell-based replicon system. The approach described herein can be extended to the synthesis of the bisulfite adducts of other classes of transition state inhibitors of serine and cysteine proteases, such as alpha-ketoheterocycles and alpha-ketoesters. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.026
• 作为产物：
  描述：

  L-环己基丙氨酸甲酯盐酸盐 在 锂硼氢 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 Cbz-Cha-Ala(2-oxopyrrolidin-3-yl)(2-oxopyrrolidin-3-yl)-ol
  参考文献：
  名称：

  Potent inhibition of norovirus by dipeptidyl α-hydroxyphosphonate transition state mimics

  摘要：

  The design, synthesis, and evaluation of a series of dipeptidyl alpha-hydroxyphosphonates is reported. The synthesized compounds displayed high anti-norovirus activity in a cell-based replicon system, as well as high enzyme selectivity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.073

文献信息

• Structure-Guided Design and Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease. Structure–Activity Relationships and Biochemical, X-ray Crystallographic, Cell-Based, and In Vivo Studies
  作者：Anushka C. Galasiti Kankanamalage、Yunjeong Kim、Pathum M. Weerawarna、Roxanne Adeline Z. Uy、Vishnu C. Damalanka、Sivakoteswara Rao Mandadapu、Kevin R. Alliston、Nurjahan Mehzabeen、Kevin P. Battaile、Scott Lovell、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1021/jm5019934

  日期：2015.4.9

  Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus 3C-like protease is essential for viral replication, consequently, inhibition of this enzyme is a fruitful avenue of investigation that may lead to the emergence of antinorovirus therapeutics. We describe herein the optimization of dipeptidyl inhibitors of norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an inhibitor using the murine model of norovirus infection.