(4S)-4-[N-(tert-butoxycarbonyl)amino]-5-hydroxypentannoic acid (N,N-dimethyl)amide | 1345825-92-4

• 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: (4S)-4-[N-(tert-butoxycarbonyl)amino]-5-hydroxypentannoic acid (N,N-dimethyl)amide
• 英文别名: Boc-Gln(Me)2-ol；tert-butyl N-[(2S)-5-(dimethylamino)-1-hydroxy-5-oxopentan-2-yl]carbamate
• CAS: 1345825-92-4
• 化学式: C₁₂H₂₄N₂O₄
• 分子量: 260.334
• InChiKey: UTHQQZDRXVTWAZ-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S)-4-[N-(tert-butoxycarbonyl)amino]-5-hydroxypentannoic acid (N,N-dimethyl)amide 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以41%的产率得到(4S)-N,N-dimethyl-4-(tert-butyloxycarbonylamino)-5-oxopentanamide
  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：

  N²-(tert-butyloxycarbonyl)-N⁵,N⁵-dimethylglutamine benzyl ester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以72%的产率得到(4S)-4-[N-(tert-butoxycarbonyl)amino]-5-hydroxypentannoic acid (N,N-dimethyl)amide
  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.