N-[(1S)-1-[[[(1S)-1-(羟基甲基)-2-(2-氧代-3-吡咯烷基)乙基]氨基]羰基]-3-甲基丁基]氨基甲酸苄酯 | 1333231-43-8

• 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
• 中文名称: N-[(1S)-1-[[[(1S)-1-(羟基甲基)-2-(2-氧代-3-吡咯烷基)乙基]氨基]羰基]-3-甲基丁基]氨基甲酸苄酯
• 英文名称: Benzyl ((2S)-1-(((2S)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)carbamate
• 英文别名: benzyl N-[(2S)-1-[[(2S)-1-hydroxy-3-(2-oxopyrrolidin-3-yl)propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
• CAS: 1333231-43-8
• 化学式: C₂₁H₃₁N₃O₅
• 分子量: 405.494
• InChiKey: JUCVXDDMQHPCKT-FQECFTEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  29
• 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：
  5

反应信息

• 作为反应物：
  描述：

  N-[(1S)-1-[[[(1S)-1-(羟基甲基)-2-(2-氧代-3-吡咯烷基)乙基]氨基]羰基]-3-甲基丁基]氨基甲酸苄酯 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 benzyl ((S)-4-methyl-1-oxo-1-(((S)-1-oxo-3-(2-oxopyrrolidin-3-yl)propan-2-yl)amino)pentan-2-yl)carbamate
  参考文献：
  名称：

  [EN] MACROCYCLIC AND PEPTIDOMIMETIC COMPOUNDS AS BROAD-SPECTRUM ANTIVIRALS AGAINST 3C OR 3C-LIKE PROTEASES OF PICORNAVIRUSES, CALICIVIRUSES AND CORONAVIRUSES
  [FR] COMPOSÉS MACROCYCLIQUES ET PEPTIDOMIMÉTIQUES EN TANT QU'ANTIVIRAUX À LARGE SPECTRE CONTRE DES PROTÉASES 3C OU DE TYPE 3C DE PICORNAVIRUS, CALICIVIRUS ET CORONAVIRUS

  摘要：

  抗病毒蛋白酶抑制剂，包括大环过渡态抑制剂和肽类模拟物，以及相关的抗病毒化合物和使用这些化合物治疗或预防病毒感染和疾病的方法被披露。这些化合物对属于小RNA病毒超簇的病毒具有广谱活性，包括重要的人类和动物病原体，如诺如病毒、沙波病毒、肠病毒、脊髓灰质炎病毒、口蹄疫病毒、甲型肝炎病毒、人类鼻病毒（普通感冒的原因之一）、人类冠状病毒（另一种普通感冒的原因）、可传染性胃肠炎病毒、小鼠肝炎病毒、猫传染性腹膜炎病毒和严重急性呼吸综合征冠状病毒等。

  公开号：

  WO2013166319A1
• 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 N-[(1S)-1-[[[(1S)-1-(羟基甲基)-2-(2-氧代-3-吡咯烷基)乙基]氨基]羰基]-3-甲基丁基]氨基甲酸苄酯
  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

• [EN] MACROCYCLIC AND PEPTIDOMIMETIC COMPOUNDS AS BROAD-SPECTRUM ANTIVIRALS AGAINST 3C OR 3C-LIKE PROTEASES OF PICORNAVIRUSES, CALICIVIRUSES AND CORONAVIRUSES<br/>[FR] COMPOSÉS MACROCYCLIQUES ET PEPTIDOMIMÉTIQUES EN TANT QU'ANTIVIRAUX À LARGE SPECTRE CONTRE DES PROTÉASES 3C OU DE TYPE 3C DE PICORNAVIRUS, CALICIVIRUS ET CORONAVIRUS
  申请人：UNIV KANSAS STATE

  公开号：WO2013166319A1

  公开（公告）日：2013-11-07

  Antiviral protease inhibitors, including macrocylic transition state inhibitors and peptidomimetics are disclosed, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease. The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, sapoviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus.

  抗病毒蛋白酶抑制剂，包括大环过渡态抑制剂和肽类模拟物，以及相关的抗病毒化合物和使用这些化合物治疗或预防病毒感染和疾病的方法被披露。这些化合物对属于小RNA病毒超簇的病毒具有广谱活性，包括重要的人类和动物病原体，如诺如病毒、沙波病毒、肠病毒、脊髓灰质炎病毒、口蹄疫病毒、甲型肝炎病毒、人类鼻病毒（普通感冒的原因之一）、人类冠状病毒（另一种普通感冒的原因）、可传染性胃肠炎病毒、小鼠肝炎病毒、猫传染性腹膜炎病毒和严重急性呼吸综合征冠状病毒等。
• 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.
• Potent inhibition of norovirus by dipeptidyl α-hydroxyphosphonate transition state mimics
  作者：Sivakoteswara Rao Mandadapu、Mallikarjuna Reddy Gunnam、Anushka C. Galasiti Kankanamalage、Roxanne Adeline Z. Uy、Kevin R. Alliston、Gerald H. Lushington、Yunjeong Kim、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1016/j.bmcl.2013.08.073

  日期：2013.11

  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.
• Potent inhibition of norovirus 3CL protease by peptidyl α-ketoamides and α-ketoheterocycles
  作者：Sivakoteswara Rao Mandadapu、Pathum M. Weerawarna、Mallikarjuna Reddy Gunnam、Kevin R. Alliston、Gerald H. Lushington、Yunjeong Kim、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1016/j.bmcl.2012.05.055

  日期：2012.7

  A series of structurally-diverse alpha-ketoamides and alpha-ketoheterocycles was synthesized and subsequently investigated for inhibitory activity against norovirus 3CL protease in vitro, as well as anti-norovirus activity in a cell-based replicon system. The synthesized compounds were found to inhibit norovirus 3CL protease in vitro and to also exhibit potent anti-norovirus activity in a cell-based replicon system. (C) 2012 Elsevier Ltd. All rights reserved.
• Design, synthesis, and evaluation of inhibitors of Norwalk virus 3C protease
  作者：Kok-Chuan Tiew、Guijia He、Sridhar Aravapalli、Sivakoteswara Rao Mandadapu、Mallikarjuna Reddy Gunnam、Kevin R. Alliston、Gerald H. Lushington、Yunjeong Kim、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1016/j.bmcl.2011.07.016

  日期：2011.9

  The first series of peptidyl aldehyde inhibitors that incorporate in their structure a glutamine surrogate has been designed and synthesized based on the known substrate specificity of Norwalk virus 3C protease. The inhibitory activity of the compounds with the protease and with a norovirus cell-based replicon system was investigated. Members of this class of compounds exhibited noteworthy activity both in vitro and in a cell-based replicon system. (C) 2011 Elsevier Ltd. All rights reserved.