tert-butyl N-(4-{[2-(Benzotriazol-1-yl)acetyl]-(3-thienylmethyl)amino}phenyl)carbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl N-(4-{[2-(Benzotriazol-1-yl)acetyl]-(3-thienylmethyl)amino}phenyl)carbamate
• 英文别名: tert-butyl N-[4-[[2-(benzotriazol-1-yl)acetyl]-(thiophen-3-ylmethyl)amino]phenyl]carbamate
• 化学式: C₂₄H₂₅N₅O₃S
• 分子量: 463.56
• InChiKey: WFYKLZZEIZEDEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl N-(4-{[2-(Benzotriazol-1-yl)acetyl]-(3-thienylmethyl)amino}phenyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以95%的产率得到N-(4-aminophenyl)-2-(benzotriazol-1-yl)-N-(3-thienylmethyl)acetamide
  参考文献：
  名称：

  Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: Identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding

  摘要：

  Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2-S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond.

  DOI：

  10.1016/j.bmcl.2013.08.112
• 作为产物：
  描述：

  特定基氨基甲酸脂酶 在 三乙酰氧基硼氢化钠 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl N-(4-{[2-(Benzotriazol-1-yl)acetyl]-(3-thienylmethyl)amino}phenyl)carbamate
  参考文献：
  名称：

  Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: Identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding

  摘要：

  Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2-S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond.

  DOI：

  10.1016/j.bmcl.2013.08.112

文献信息

• Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: Identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding
  作者：Mark Turlington、Aspen Chun、Sakshi Tomar、Aimee Eggler、Valerie Grum-Tokars、Jon Jacobs、J. Scott Daniels、Eric Dawson、Adrian Saldanha、Peter Chase、Yahira M. Baez-Santos、Craig W. Lindsley、Peter Hodder、Andrew D. Mesecar、Shaun R. Stauffer

  DOI：10.1016/j.bmcl.2013.08.112

  日期：2013.11

  Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2-S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond.
• [EN] PROTEASE INHIBITORS AND METHODS OF USE<br/>[FR] INHIBITEURS DE PROTÉASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：[en]THE CLEVELAND CLINIC FOUNDATION

  公开号：WO2022226203A1

  公开（公告）日：2022-10-27

  Disclosed herein are compounds that inhibit 3C-like protease and inhibit replication of viruses, including SARS-CoV-2. Also disclosed herein are pharmaceutical compositions comprising the compounds, and methods of using the compounds, e.g., in a method of treating a viral infection, such as a coronavirus infection.
• Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CL^pro)
  作者：Sang Hoon Han、Christopher M. Goins、Tarun Arya、Woo-Jin Shin、Joshua Maw、Alice Hooper、Dhiraj P. Sonawane、Matthew R. Porter、Breyanne E. Bannister、Rachel D. Crouch、A. Abigail Lindsey、Gabriella Lakatos、Steven R. Martinez、Joseph Alvarado、Wendell S. Akers、Nancy S. Wang、Jae U. Jung、Jonathan D. Macdonald、Shaun R. Stauffer

  DOI：10.1021/acs.jmedchem.1c00598

  日期：2022.2.24