[1-(Cyano-hydroxy-methyl)-3-methyl-butyl]-carbamic acid tert-butyl ester | 119624-36-1

• 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-(Cyano-hydroxy-methyl)-3-methyl-butyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-(1-cyano-1-hydroxy-4-methylpentan-2-yl)carbamate
• CAS: 119624-36-1
• 化学式: C₁₂H₂₂N₂O₃
• 分子量: 242.318
• InChiKey: XGLQRBUIBGGNOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [1-(Cyano-hydroxy-methyl)-3-methyl-butyl]-carbamic acid tert-butyl ester 在 盐酸 、 lithium hydroxide 、 双氧水 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 (S)-3-Amino-(R)-2-hydroxy-5-methylhexanamide hydrochloride
  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
• 作为产物：
  描述：

  乙基L-亮氨酸酯 在 N-甲基吗啉 、 lithium hydroxide 、 lithium aluminium tetrahydride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 [1-(Cyano-hydroxy-methyl)-3-methyl-butyl]-carbamic acid tert-butyl ester
  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 inhibitors of hepatitis C NS3–NS4A serine protease derived from 2-aza-bicyclo[2.2.1]heptane-3-carboxylic acid
  作者：Srikanth Venkatraman、F. George Njoroge、Wanli Wu、Viyyoor Girijavallabhan、Andrew J. Prongay、Nancy Butkiewicz、John Pichardo

  DOI：10.1016/j.bmcl.2005.12.046

  日期：2006.3

  Prolonged hepatitis C infection is the leading cause for cirrhosis of the liver and hepatocellular carcinoma. The etiological agent HCV virus codes a single polyprotein of similar to 3000 amino acids that is processed with the help of a serine protease NS3A to produce structural and non-structural proteins required for viral replication. Inhibition of NS3 protease can potentially be used to develop drugs for treatment of HCV infections. Herein, we report the development of a series of novel NS3 serine protease inhibitors derived from 2-aza-bicyclo[2.2.1]-heptane carboxylic acid with potential therapeutic use for treatment of HCV infections. (C) 2005 Elsevier Ltd. All rights reserved.
• USRE40901E1
  申请人：——

  公开号：USRE40901E1

  公开（公告）日：2009-09-01