1,1-dimethylethyl-[2-[(1R,5S)-2(S)-[[[1-(2-amino-1,2-dioxoethyl)butyl]amino]carbonyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hex-3-yl]-1(S)-cyclohexyl-2-oxoethyl]carbamate

• 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: 1,1-dimethylethyl-[2-[(1R,5S)-2(S)-[[[1-(2-amino-1,2-dioxoethyl)butyl]amino]carbonyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hex-3-yl]-1(S)-cyclohexyl-2-oxoethyl]carbamate
• 英文别名: tert-butyl N-[(1S)-2-[(1R,2S,5S)-2-[(1-carbamoyl-1-oxopentan-2-yl)carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-1-cyclohexyl-2-oxoethyl]carbamate；tert-butyl N-[(1S)-2-[(1R,2S,5S)-2-[(1-amino-1,2-dioxohexan-3-yl)carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-1-cyclohexyl-2-oxoethyl]carbamate
• 化学式: C₂₇H₄₄N₄O₆
• 分子量: 520.67
• InChiKey: ANWXAHDHVAGJFL-CRJJDSQLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-hydroxy-3-nitrohexanoic acid 在 palladium on activated charcoal 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 N-甲基吗啉 、 盐酸 、 二氯乙酸 、 氢气 、 碳酸氢钠 、 氯化铵 、 溶剂黄146 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 1,1-dimethylethyl-[2-[(1R,5S)-2(S)-[[[1-(2-amino-1,2-dioxoethyl)butyl]amino]carbonyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hex-3-yl]-1(S)-cyclohexyl-2-oxoethyl]carbamate
  参考文献：
  名称：

  Discovery of (1R,5S)-N-[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor:  A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection

  摘要：

  Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.

  DOI：

  10.1021/jm060325b

文献信息

• NOVEL PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS
  申请人：Saksena Anil K.

  公开号：US20110117057A1

  公开（公告）日：2011-05-19

  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.

  本发明披露了具有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，本发明披露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。
• US7244721B2
  申请人：——

  公开号：US7244721B2

  公开（公告）日：2007-07-17
• US7592316B2
  申请人：——

  公开号：US7592316B2

  公开（公告）日：2009-09-22
• USRE43298E1
  申请人：——

  公开号：USRE43298E1

  公开（公告）日：2012-04-03