benzyl (9-formyl-12-isobutyl-6,11,14-trioxo-1,5,10,13,18,19-hexaazabicyclo[15.2.1]icosa-17(20),18-dien-15-yl)carbamate | 1443654-67-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: benzyl (9-formyl-12-isobutyl-6,11,14-trioxo-1,5,10,13,18,19-hexaazabicyclo[15.2.1]icosa-17(20),18-dien-15-yl)carbamate
• 英文别名: benzyl ((3S,6S,9S,Z)-9-formyl-6-isobutyl-4,7,12-trioxo-1¹H-5,8,13-triaza-1(4,1)-triazolacyclohexadecaphane-3-yl)carbamate；benzyl N-[(9S,12S,15S)-9-formyl-12-(2-methylpropyl)-6,11,14-trioxo-1,5,10,13,18,19-hexazabicyclo[15.2.1]icosa-17(20),18-dien-15-yl]carbamate
• CAS: 1443654-67-8
• 化学式: C₂₇H₃₇N₇O₆
• 分子量: 555.634
• InChiKey: WWUVWAHYMWQCIM-PMVMPFDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  40
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  173
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-L-谷氨酸 1-甲酯 在 盐酸 、 锂硼氢 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 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 、 copper(I) bromide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 benzyl (9-formyl-12-isobutyl-6,11,14-trioxo-1,5,10,13,18,19-hexaazabicyclo[15.2.1]icosa-17(20),18-dien-15-yl)carbamate
  参考文献：
  名称：

  Macrocyclic inhibitors of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus

  摘要：

  The design, synthesis, and in vitro evaluation of the first macrocyclic inhibitor of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus are reported. The in vitro inhibitory activity (50% effective concentration) of the macrocyclic inhibitor toward enterovirus 3C protease (CVB3 Nancy strain), and coronavirus (SARS-CoV) and norovirus 3C-like proteases, was determined to be 1.8, 15.5 and 5.1 mu M, respectively. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.021

文献信息

• Structure-based design and synthesis of triazole-based macrocyclic inhibitors of norovirus protease: Structural, biochemical, spectroscopic, and antiviral studies
  作者：Pathum M. Weerawarna、Yunjeong Kim、Anushka C. Galasiti Kankanamalage、Vishnu C. Damalanka、Gerald H. Lushington、Kevin R. Alliston、Nurjahan Mehzabeen、Kevin P. Battaile、Scott Lovell、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1016/j.ejmech.2016.04.013

  日期：2016.8

  effective strategy for the development of norovirus therapeutics entails the discovery of inhibitors of norovirus 3CL protease, an enzyme essential for noroviral replication. We describe herein the structure-based design of the first class of permeable, triazole-based macrocyclic inhibitors of norovirus 3C-like protease, as well as pertinent X-ray crystallographic, biochemical, spectroscopic, and antiviral

  由诺如病毒引起的急性肠胃炎暴发构成了全世界的公共卫生问题。迄今为止，尚无获批用于管理和预防诺如病毒感染的药物或疫苗。开发诺如病毒疗法的潜在有效策略需要发现诺如病毒 3CL 蛋白酶的抑制剂，这是一种对诺如病毒复制至关重要的酶。我们在此描述了基于结构的第一类诺如病毒 3C 样蛋白酶的可渗透、三唑基大环抑制剂的设计，以及相关的 X 射线晶体学、生化、光谱和抗病毒研究。
• [EN] MACROCYCLIC AND PEPTIDOMIMETIC COMPOUNDS AS BROAD-SPECTRUM ANTIVIRALS AGAINST 3C OR 3C-LIKE PROTEASES OF PICORNAVIRUSES, CALICIVIRUSES AND CORONAVIRUSES<br/>[FR] COMPOSÉS MACROCYCLIQUES ET PEPTIDOMIMÉTIQUES EN TANT QU'ANTIVIRAUX À LARGE SPECTRE CONTRE DES PROTÉASES 3C OU DE TYPE 3C DE PICORNAVIRUS, CALICIVIRUS ET CORONAVIRUS
  申请人：UNIV KANSAS STATE

  公开号：WO2013166319A1

  公开（公告）日：2013-11-07

  Antiviral protease inhibitors, including macrocylic transition state inhibitors and peptidomimetics are disclosed, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease. The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, sapoviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus.

  抗病毒蛋白酶抑制剂，包括大环过渡态抑制剂和肽类模拟物，以及相关的抗病毒化合物和使用这些化合物治疗或预防病毒感染和疾病的方法被披露。这些化合物对属于小RNA病毒超簇的病毒具有广谱活性，包括重要的人类和动物病原体，如诺如病毒、沙波病毒、肠病毒、脊髓灰质炎病毒、口蹄疫病毒、甲型肝炎病毒、人类鼻病毒（普通感冒的原因之一）、人类冠状病毒（另一种普通感冒的原因）、可传染性胃肠炎病毒、小鼠肝炎病毒、猫传染性腹膜炎病毒和严重急性呼吸综合征冠状病毒等。
• MACROCYCLIC AND PEPTIDOMIMETIC COMPOUNDS AS BROAD-SPECTRUM ANTIVIRALS AGAINST 3C OR 3C-LIKE PROTEASES OF PICORNAVIRUSES, CALICIVIRUSES AND CORONAVIRUSES
  申请人：Kansa State University Research Foundation

  公开号：US20150133368A1

  公开（公告）日：2015-05-14

  Antiviral protease inhibitors, including macrocylic transition state inhibitors and peptidomimetics are disclosed, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease. The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, sapoviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus.

  本文披露了抗病毒蛋白酶抑制剂，包括大环过渡态抑制剂和肽类类似物，以及相关的抗病毒化合物和使用它们治疗或预防病毒感染和疾病的方法。这些化合物对属于小RNA病毒超簇的病毒具有广谱活性，包括重要的人类和动物病原体，如诺如病毒、沙波病毒、肠道病毒、脊髓灰质炎病毒、口蹄疫病毒、甲型肝炎病毒、人类鼻病毒（普通感冒的原因之一）、人类冠状病毒（另一种普通感冒的原因）、可传播性胃肠炎病毒、小鼠肝炎病毒、猫传染性腹膜炎病毒和严重急性呼吸综合症冠状病毒。
• US9309284B2
  申请人：——

  公开号：US9309284B2

  公开（公告）日：2016-04-12
• Macrocyclic inhibitors of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus
  作者：Sivakoteswara Rao Mandadapu、Pathum M. Weerawarna、Allan M. Prior、Roxanne Adeline Z. Uy、Sridhar Aravapalli、Kevin R. Alliston、Gerald H. Lushington、Yunjeong Kim、Duy H. Hua、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1016/j.bmcl.2013.05.021

  日期：2013.7

  The design, synthesis, and in vitro evaluation of the first macrocyclic inhibitor of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus are reported. The in vitro inhibitory activity (50% effective concentration) of the macrocyclic inhibitor toward enterovirus 3C protease (CVB3 Nancy strain), and coronavirus (SARS-CoV) and norovirus 3C-like proteases, was determined to be 1.8, 15.5 and 5.1 mu M, respectively. (C) 2013 Elsevier Ltd. All rights reserved.