(S)-2-{(S)-2-[(2S,3R)-2-((S)-2-Acetylamino-3-methyl-butyrylamino)-3-benzyloxy-butyrylamino]-4-methyl-pentanoylamino}-3-((S)-2-oxo-pyrrolidin-3-yl)-propionic acid methyl ester | 813451-43-3

• 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: (S)-2-{(S)-2-[(2S,3R)-2-((S)-2-Acetylamino-3-methyl-butyrylamino)-3-benzyloxy-butyrylamino]-4-methyl-pentanoylamino}-3-((S)-2-oxo-pyrrolidin-3-yl)-propionic acid methyl ester
• 英文别名: Ac-Val-Thr(Bn)-Leu-Ala((S)-2-oxopyrrolidin-3-yl)-OMe；methyl (2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-acetamido-3-methylbutanoyl]amino]-3-phenylmethoxybutanoyl]amino]-4-methylpentanoyl]amino]-3-[(3S)-2-oxopyrrolidin-3-yl]propanoate
• CAS: 813451-43-3
• 化学式: C₃₂H₄₉N₅O₈
• 分子量: 631.77
• InChiKey: QYXRRYWRYUFABJ-VUXQNLRASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  45
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  181
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-2-{(S)-2-[(2S,3R)-2-((S)-2-Acetylamino-3-methyl-butyrylamino)-3-benzyloxy-butyrylamino]-4-methyl-pentanoylamino}-3-((S)-2-oxo-pyrrolidin-3-yl)-propionic acid methyl ester 在 lithium hydroxide 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (5S,8S,11S)-5-chloropyridin-3-yl 8-((R)-1-(benzyloxy)ethyl)-5-isobutyl-11-isopropyl-4,7,10,13-tetraoxo-2-((S)-2-oxopyrrolidin-3-yl)methyl-3,6,9,12-tetraazatetradecan-1-oate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Inhibitors for Severe Acute Respiratory Syndrome 3C-Like Protease Based on Phthalhydrazide Ketones or Heteroaromatic Esters

  摘要：

  The 3C-like protease (3CL(pro)), which controls the severe acute respiratory syndrome (SARS) coronavirus replication, has been identified as a potential target for drug design in the treatment of SARS. A series of tetrapeptide phthalhydrazide ketones, pyridinyl esters, and their analogs have been designed, synthesized, and evaluated as potential SARS 3CL(pro) inhibitors. Some pyridinyl esters are identified as very potent inhibitors, with IC50 values in the nanomolar range (50-65 nM). Electrospray mass spectrometry indicates a mechanism involving acylation of the active site cysteine thiol for this class of inhibitors.

  DOI：

  10.1021/jm061425k
• 作为产物：
  描述：

  (alphaS,3S)-alpha-[(叔-丁基氧羰基)氨基]-2-氧代-3-吡咯烷丙酸甲酯 、 Ac-Val-Thr(OBn)-Leu-OH 在 三氟乙酸 、 1-羟基苯并三唑 、 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 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以65%的产率得到(S)-2-{(S)-2-[(2S,3R)-2-((S)-2-Acetylamino-3-methyl-butyrylamino)-3-benzyloxy-butyrylamino]-4-methyl-pentanoylamino}-3-((S)-2-oxo-pyrrolidin-3-yl)-propionic acid methyl ester
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Inhibitors for Severe Acute Respiratory Syndrome 3C-Like Protease Based on Phthalhydrazide Ketones or Heteroaromatic Esters

  摘要：

  The 3C-like protease (3CL(pro)), which controls the severe acute respiratory syndrome (SARS) coronavirus replication, has been identified as a potential target for drug design in the treatment of SARS. A series of tetrapeptide phthalhydrazide ketones, pyridinyl esters, and their analogs have been designed, synthesized, and evaluated as potential SARS 3CL(pro) inhibitors. Some pyridinyl esters are identified as very potent inhibitors, with IC50 values in the nanomolar range (50-65 nM). Electrospray mass spectrometry indicates a mechanism involving acylation of the active site cysteine thiol for this class of inhibitors.

  DOI：

  10.1021/jm061425k

文献信息

• Synthesis and Evaluation of Keto-Glutamine Analogues as Potent Inhibitors of Severe Acute Respiratory Syndrome 3CL^pro
  作者：Rajendra P. Jain、Hanna I. Pettersson、Jianmin Zhang、Katherine D. Aull、Pascal D. Fortin、Carly Huitema、Lindsay D. Eltis、Jonathan C. Parrish、Michael N. G. James、David S. Wishart、John C. Vederas

  DOI：10.1021/jm0494873

  日期：2004.12.1

  The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at the a-position were synthesized and tested as reversible inhibitiors against SARS 3CL(pro). Attachment of tripeptide (Ac-Val-Thr-Leu) to these glutamine-based "warheads" generated significantly better inhibitors (4a-c, 8a-d) with IC50 values ranging from 0.60 to 70 muM.
• Design, Synthesis, and Evaluation of Inhibitors for Severe Acute Respiratory Syndrome 3C-Like Protease Based on Phthalhydrazide Ketones or Heteroaromatic Esters
  作者：Jianmin Zhang、Hanna I. Pettersson、Carly Huitema、Chunying Niu、Jiang Yin、Michael N. G. James、Lindsay D. Eltis、John C. Vederas

  DOI：10.1021/jm061425k

  日期：2007.4.1

  The 3C-like protease (3CL(pro)), which controls the severe acute respiratory syndrome (SARS) coronavirus replication, has been identified as a potential target for drug design in the treatment of SARS. A series of tetrapeptide phthalhydrazide ketones, pyridinyl esters, and their analogs have been designed, synthesized, and evaluated as potential SARS 3CL(pro) inhibitors. Some pyridinyl esters are identified as very potent inhibitors, with IC50 values in the nanomolar range (50-65 nM). Electrospray mass spectrometry indicates a mechanism involving acylation of the active site cysteine thiol for this class of inhibitors.