ethyl {(2E,4S)-4-[N-(tert-butoxycarbonyl)amino]-7-one-7-dimethylamino}-2-heptenoate | 1246669-15-7

• 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: ethyl {(2E,4S)-4-[N-(tert-butoxycarbonyl)amino]-7-one-7-dimethylamino}-2-heptenoate
• 英文别名: Boc-NHCH[CH2CH2CON(CH3)2]-CH=CHCOOC2H5
• CAS: 1246669-15-7
• 化学式: C₁₆H₂₈N₂O₅
• 分子量: 328.409
• InChiKey: XJYUYVWJATVFPF-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.87
• 重原子数：
  23.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  84.94
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl {(2E,4S)-4-[N-(tert-butoxycarbonyl)amino]-7-one-7-dimethylamino}-2-heptenoate 在 3-hydroxy-1,2,3-benzotriazine-4-one 、 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 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.33h， 生成 Ac-Ser-Ala-Val-Leu-NHCH[CH2CH2CON(CH3)2]-CH=CHCOOC2H5
  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：

  N-叔丁氧羰基-L-谷氨酸 1-苄酯 在 lithium aluminium tetrahydride 、 草酰氯 、 sodium hydride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 19.25h， 生成 ethyl {(2E,4S)-4-[N-(tert-butoxycarbonyl)amino]-7-one-7-dimethylamino}-2-heptenoate
  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