4-fluorobenzyl ((S)-1-(((S)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)carbamate | 1416992-28-3

• 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: 4-fluorobenzyl ((S)-1-(((S)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)carbamate
• 英文别名: (4-fluorophenyl)methyl N-[(2S)-1-[[(2S)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
• CAS: 1416992-28-3
• 化学式: C₂₁H₃₀FN₃O₅
• 分子量: 423.485
• InChiKey: QICMOEJMGNTZGQ-BEEDKBRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-fluorobenzyl ((S)-1-(((S)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)carbamate 在 戴斯-马丁氧化剂 、 sodium hydrogensulfite 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 sodium-(2S)-2-((S)-2-((((4-fluorobenzyl)oxy)carbonyl)amino)-4-methylpentanamido)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propane-1-sulfonate
  参考文献：
  名称：

  SARS-CoV-2 3CL 蛋白酶强效抑制剂的结构引导设计：结构、生化和细胞研究

  摘要：

  COVID-19 大流行正在对全世界的公共卫生产生重大影响，迫切需要建立有效的治疗方法，包括疫苗、生物制剂和小分子治疗方法，以对抗 SARS-CoV-2 和新兴变体。对病毒生命周期的检查揭示了多个基于病毒和宿主的阻塞点，可以利用这些阻塞点来对抗病毒。SARS-CoV-2 3C 样蛋白酶（3CLpro）是病毒复制所必需的酶，是治疗干预的一个有吸引力的靶点，蛋白酶抑制剂的设计可能会导致有效的 SARS-CoV-2 特异性药物的出现。抗病毒药物。我们在此描述了与 X 射线晶体学、索普-英戈尔德效应、氘化和立体化学在 SARS-CoV-2 3CLpro 高效无毒抑制剂设计中的应用相关的研究结果。

  DOI：

  10.1021/acs.jmedchem.1c01037
• 作为产物：
  描述：

  (S)-(-)-2-异氰酰基-4-甲基戊酸甲酯 在 锂硼氢 、 水 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-fluorobenzyl ((S)-1-(((S)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-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

文献信息

• Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors
  作者：Sivakoteswara Rao Mandadapu、Mallikarjuna Reddy Gunnam、Kok-Chuan Tiew、Roxanne Adeline Z. Uy、Allan M. Prior、Kevin R. Alliston、Duy H. Hua、Yunjeong Kim、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1016/j.bmcl.2012.11.026

  日期：2013.1

  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.
• Structure-Guided Design of Potent Inhibitors of SARS-CoV-2 3CL Protease: Structural, Biochemical, and Cell-Based Studies
  作者：Chamandi S. Dampalla、Athri D. Rathnayake、Krishani Dinali Perera、Abdul-Rahman M. Jesri、Harry Nhat Nguyen、Matthew J. Miller、Hayden A. Thurman、Jian Zheng、Maithri M. Kashipathy、Kevin P. Battaile、Scott Lovell、Stanley Perlman、Yunjeong Kim、William C. Groutas、Kyeong-Ok Chang

  DOI：10.1021/acs.jmedchem.1c01037

  日期：2021.12.23

  target for therapeutic intervention, and the design of inhibitors of the protease may lead to the emergence of effective SARS-CoV-2-specific antivirals. We describe herein the results of our studies related to the application of X-ray crystallography, the Thorpe–Ingold effect, deuteration, and stereochemistry in the design of highly potent and nontoxic inhibitors of SARS-CoV-2 3CLpro.

  COVID-19 大流行正在对全世界的公共卫生产生重大影响，迫切需要建立有效的治疗方法，包括疫苗、生物制剂和小分子治疗方法，以对抗 SARS-CoV-2 和新兴变体。对病毒生命周期的检查揭示了多个基于病毒和宿主的阻塞点，可以利用这些阻塞点来对抗病毒。SARS-CoV-2 3C 样蛋白酶（3CLpro）是病毒复制所必需的酶，是治疗干预的一个有吸引力的靶点，蛋白酶抑制剂的设计可能会导致有效的 SARS-CoV-2 特异性药物的出现。抗病毒药物。我们在此描述了与 X 射线晶体学、索普-英戈尔德效应、氘化和立体化学在 SARS-CoV-2 3CLpro 高效无毒抑制剂设计中的应用相关的研究结果。