(2S)-2-amino-3-(2-oxopyrrolidin-3-yl)propanoic acid methyl ester hydrochloride | 1385184-01-9

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物 - 羧酸酯及其衍生物
• 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: (2S)-2-amino-3-(2-oxopyrrolidin-3-yl)propanoic acid methyl ester hydrochloride
• 英文别名: methyl (2S)-2-amino-3-(2-oxopyrrolidin-3-yl)propanoate hydrochloride；methyl (2S)-2-amino-3-(2-oxopyrrolidin-3-yl)propanoate;hydrochloride
• CAS: 1385184-01-9
• 化学式: C₈H₁₄N₂O₃*ClH
• 分子量: 222.672
• InChiKey: XFJBHQSJYHXLGJ-PQAGPIFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.57
• 重原子数：
  14.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  81.42
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-3-(2-oxopyrrolidin-3-yl)propanoic acid methyl ester hydrochloride 在 锂硼氢 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 Cbz-Phe-Ala(2-oxopyrrolidin-3-yl)(2-oxopyrrolidin-3-yl)-al
  参考文献：
  名称：

  Potent inhibition of norovirus 3CL protease by peptidyl α-ketoamides and α-ketoheterocycles

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.05.055
• 作为产物：
  描述：

  (2S)-2-((叔丁氧基羰基)氨基)-3-(2-氧代吡咯烷-3-基)丙酸甲酯 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 (2S)-2-amino-3-(2-oxopyrrolidin-3-yl)propanoic acid methyl ester hydrochloride
  参考文献：
  名称：

  Potent inhibition of norovirus 3CL protease by peptidyl α-ketoamides and α-ketoheterocycles

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.05.055

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。
• 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。
• 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.
• 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.