(1R,5S)-N-[3-(cyclopropylamino)-1(S)-(2-cyclopropylethyl)-2,3-dioxopropyl]-3-[2(S)-[[[[1-[[[cycloppropyl(methyl)amino]sulfonyl]methyl]cyclohexyl]amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl-3-azabicyclo[3.1.0]-hexane-2(S)-carboxamide | 946834-71-5

• 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: (1R,5S)-N-[3-(cyclopropylamino)-1(S)-(2-cyclopropylethyl)-2,3-dioxopropyl]-3-[2(S)-[[[[1-[[[cycloppropyl(methyl)amino]sulfonyl]methyl]cyclohexyl]amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl-3-azabicyclo[3.1.0]-hexane-2(S)-carboxamide
• 英文别名: (1R,5S)-N-((S)-5-cyclopropyl-1-(cyclopropylamino)-1,2-dioxopentan-3-yl)-3-((S)-2-(3-(1-((N-cyclopropyl-N-methylsulfamoyl)methyl)cyclohexyl)ureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide；(1S,4S,5R)-N-[(1S)-3-(cyclopropylamino)-1-(2-cyclopropylethyl)-2,3-dioxo-propyl]-3-[(2S)-2-[[1-[[cyclopropyl(methyl)sulfamoyl]methyl]cyclohexyl]carbamoylamino]-3,3-dimethyl-butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-4-carboxamide；(1R,2S,5S)-N-[(3S)-5-cyclopropyl-1-(cyclopropylamino)-1,2-dioxopentan-3-yl]-3-[(2S)-2-[[1-[[cyclopropyl(methyl)sulfamoyl]methyl]cyclohexyl]carbamoylamino]-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
• CAS: 946834-71-5
• 化学式: C₃₇H₆₀N₆O₇S
• 分子量: 732.985
• InChiKey: KNUBMPGBZFKFKF-LOLMJFKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  183
• 氢给体数：
  4
• 氢受体数：
  8

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， 反应 3.0h， 以1 g的产率得到(1R,5S)-N-[3-(cyclopropylamino)-1(S)-(2-cyclopropylethyl)-2,3-dioxopropyl]-3-[2(S)-[[[[1-[[[cycloppropyl(methyl)amino]sulfonyl]methyl]cyclohexyl]amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl-3-azabicyclo[3.1.0]-hexane-2(S)-carboxamide
  参考文献：
  名称：

  Discovery of potent sulfonamide P4-capped ketoamide second generation inhibitors of hepatitis C virus NS3 serine protease with favorable pharmacokinetic profiles in preclinical species

  摘要：

  Hepatitis is a disease characterized by inflammation of the liver, usually producing swelling and, in many cases, permanent damage to liver tissues. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically 3% of the world's population. Boceprevir, SCH 503034, (1) our first generation HCV inhibitor, has already established proof-of-concept and is currently in late stage (phase III) clinical trials. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P-4 pocket by introducing a new sulfonamide moiety and optimization of the P1/P-1' capping led to the discovery of a novel series of inhibitors of the HCV NS3 serine protease. Optimization of the P-1 residue significantly improved potency and selectivity. The combination of optimal moieties led to the discovery of compound 47 which, in addition to being a potent inhibitor of HCV subgenomic RNA replication, was also found to have good PK profile in rat, dog and monkey. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.044

文献信息

• SULFUR COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE
  申请人：Velazquez Francisco

  公开号：US20070197448A1

  公开（公告）日：2007-08-23

  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制药组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• US7816326B2
  申请人：——

  公开号：US7816326B2

  公开（公告）日：2010-10-19