Ac-Ser-Ala-Val-Leu-His-H | 1271932-54-7

• 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: Ac-Ser-Ala-Val-Leu-His-H
• 英文别名: Ac-Ser-Ala-Val-Leu-His-al；(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-N-[(2S)-1-(1H-imidazol-5-yl)-3-oxopropan-2-yl]-4-methylpentanamide
• CAS: 1271932-54-7
• 化学式: C₂₅H₄₁N₇O₇
• 分子量: 551.643
• InChiKey: AEYIBAPLFDNVGD-JMMIECQRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  39
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  212
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  Fmoc-L-缬氨酸 、 Fmoc-L-亮氨酸 、 Fmoc-L-丙氨酸 、 FMOC-O-叔丁基-L-丝氨酸 、 乙酸酐 、 N-芴甲氧羰基-L-组氨酸 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以4.4%的产率得到Ac-Ser-Ala-Val-Leu-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

文献信息

• Peptidomimetics for the treatment of coronavirus and picornavirus infections
  申请人：Emory University

  公开号：US11207370B2

  公开（公告）日：2021-12-28

  Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV-2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus.

  用于预防、治疗或治愈人类或其他动物宿主冠状病毒、皮卡病毒和/或肝病毒科病毒感染的化合物、组合物和方法。可治疗的特定病毒包括肠道病毒。在一个实施方案中，化合物可用于治疗严重急性呼吸系统综合征病毒感染，如人冠状病毒 229E、SARS、MERS、SARS-CoV-1（OC43）和 SARS-CoV-2。在另一个实施方案中，这些方法用于治疗合并感染两种或两种以上这些病毒的患者，或合并感染一种或多种这些病毒和诺如病毒的患者。
• PEPTIDOMIMETICS FOR THE TREATMENT OF CORONAVIRUS AND PICORNAVIRUS INFECTIONS
  申请人：Emory University

  公开号：US20210008150A1

  公开（公告）日：2021-01-14

  Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV-2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus.
• 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.