(1R,2S,5S)-3-[(2S)-2-[[1-[(1R)-1-tert-butylsulfonylethyl]cyclohexyl]carbamoylamino]-2-(1-methylcyclohexyl)acetyl]-N-[(1S,2R)-1-[2-(cyclopropylamino)-2-oxoacetyl]-2-ethylcyclopropyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide | 1101837-64-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机碳酸及其衍生物
• 英文名称: (1R,2S,5S)-3-[(2S)-2-[[1-[(1R)-1-tert-butylsulfonylethyl]cyclohexyl]carbamoylamino]-2-(1-methylcyclohexyl)acetyl]-N-[(1S,2R)-1-[2-(cyclopropylamino)-2-oxoacetyl]-2-ethylcyclopropyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
• CAS: 1101837-64-2
• 化学式: C₄₀H₆₅N₅O₇S
• 分子量: 760.051
• InChiKey: PHULFRRJFPEECL-SDDDCJAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  53
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  179
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成 、 (1R,2S,5S)-3-[(2S)-2-[[1-[(1R)-1-tert-butylsulfonylethyl]cyclohexyl]carbamoylamino]-2-(1-methylcyclohexyl)acetyl]-N-[(1S,2R)-1-[2-(cyclopropylamino)-2-oxoacetyl]-2-ethylcyclopropyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
  参考文献：
  名称：

  Potent ketoamide inhibitors of HCV NS3 protease derived from quaternized P1 groups

  摘要：

  Blood borne hepatitis C infections are the primary cause for liver cirrhosis and hepatocellular carcinoma. HCV NS3 protease, a pivotal enzyme in the replication cycle of HCV virus has been the primary target for development of new drug candidates. Boceprevir and telaprevir are two novel ketoamide derived inhibitors that are currently undergoing phase-III clinical trials. These inhibitors include ketoamide functionality as serine trap and have an acidic alpha-ketoamide center that undergoes epimerization under physiological conditions. Our initial attempts to arrest this epimerization by introducing quaternary amino acids at P-1 had resulted in significantly diminished activity. In this manuscript we describe alpha quaternized P-1 group that result in potent inhibitors in the enzyme assay and demonstrate cellular activity comparable to boceprevir. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.051

文献信息

• P1-NONEPIMERIZABLE KETOAMIDE INHIBITORS OF HCV NS3 PROTEASE
  申请人：Venkatraman Srikanth

  公开号：US20100074867A1

  公开（公告）日：2010-03-25

  The present invention discloses novel compounds, which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明揭示了具有HCV蛋白酶抑制活性的新化合物，以及制备这些化合物的方法。在另一种实施方式中，本发明揭示了包含这些化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。