Ac-Ala-Val-Cha-His-(SEt)2 | 1345826-06-3

• 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: Ac-Ala-Val-Cha-His-(SEt)2
• 英文别名: (2S)-2-[[(2S)-2-acetamidopropanoyl]amino]-N-[(2S)-1-[[(2S)-1,1-bis(ethylsulfanyl)-3-(1H-imidazol-5-yl)propan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-3-methylbutanamide
• CAS: 1345826-06-3
• 化学式: C₂₉H₅₀N₆O₄S₂
• 分子量: 610.886
• InChiKey: LHAAUPRSGLCDGJ-KMAVCZJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  41
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  196
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Ac-Ala-Val-Cha-His-(SEt)2 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.02h， 以43%的产率得到Ac-Ala-Val-Cha-His-H
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Evaluation of Peptide-Mimetic SARS 3CL Protease Inhibitors

  摘要：

  The design and evaluation of low molecular weight peptide-based severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CL) protease inhibitors are described. A substrate-based peptide aldehyde was selected as a starting compound, and optimum side-chain structures were determined, based on a comparison of inhibitory activities with Michael type inhibitors. For the efficient screening of peptide aldehydes containing a specific C-terminal residue, a new approach employing thioacetal to aldehyde conversion mediated by N-bromosuccinimide was devised. Structural optimization was carried out based on X-ray crystallographic analyses of the R1881 SARS 3CL protease in a complex with each inhibitor to provide a tetrapeptide aldehyde with an IC50 value of 98 nM. The resulting compound carried no substrate sequence, except for a P-3 site directed toward the outside of the protease. X-ray crystallography provided insights into the protein-ligand interactions.

  DOI：

  10.1021/jm200870n
• 作为产物：
  描述：

  8-[2-[(1S)-1-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamidopropanoyl]amino]-3-methylbutanoyl]amino]-3-cyclohexylpropanoyl]amino]-2-(1H-imidazol-5-yl)ethyl]-1,3-dioxolan-4-yl]octanamide 、 乙硫醇 在 三氟化硼乙醚 作用下， 以 溶剂黄146 为溶剂， 反应 2.0h， 以82%的产率得到Ac-Ala-Val-Cha-His-(SEt)2
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Evaluation of Peptide-Mimetic SARS 3CL Protease Inhibitors

  摘要：

  The design and evaluation of low molecular weight peptide-based severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CL) protease inhibitors are described. A substrate-based peptide aldehyde was selected as a starting compound, and optimum side-chain structures were determined, based on a comparison of inhibitory activities with Michael type inhibitors. For the efficient screening of peptide aldehydes containing a specific C-terminal residue, a new approach employing thioacetal to aldehyde conversion mediated by N-bromosuccinimide was devised. Structural optimization was carried out based on X-ray crystallographic analyses of the R1881 SARS 3CL protease in a complex with each inhibitor to provide a tetrapeptide aldehyde with an IC50 value of 98 nM. The resulting compound carried no substrate sequence, except for a P-3 site directed toward the outside of the protease. X-ray crystallography provided insights into the protein-ligand interactions.

  DOI：

  10.1021/jm200870n

文献信息

• Structure-Based Design, Synthesis, and Evaluation of Peptide-Mimetic SARS 3CL Protease Inhibitors
  作者：Kenichi Akaji、Hiroyuki Konno、Hironori Mitsui、Kenta Teruya、Yasuhiro Shimamoto、Yasunao Hattori、Takeshi Ozaki、Masami Kusunoki、Akira Sanjoh

  DOI：10.1021/jm200870n

  日期：2011.12.8

  The design and evaluation of low molecular weight peptide-based severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CL) protease inhibitors are described. A substrate-based peptide aldehyde was selected as a starting compound, and optimum side-chain structures were determined, based on a comparison of inhibitory activities with Michael type inhibitors. For the efficient screening of peptide aldehydes containing a specific C-terminal residue, a new approach employing thioacetal to aldehyde conversion mediated by N-bromosuccinimide was devised. Structural optimization was carried out based on X-ray crystallographic analyses of the R1881 SARS 3CL protease in a complex with each inhibitor to provide a tetrapeptide aldehyde with an IC50 value of 98 nM. The resulting compound carried no substrate sequence, except for a P-3 site directed toward the outside of the protease. X-ray crystallography provided insights into the protein-ligand interactions.