3-[(2S)-2-isocyanato-3,3-dimethylbutyl]-3-azabicyclo[3.2.1]octane-2,4-dione | 848777-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 3-[(2S)-2-isocyanato-3,3-dimethylbutyl]-3-azabicyclo[3.2.1]octane-2,4-dione
• CAS: 848777-83-3
• 化学式: C₁₄H₂₀N₂O₃
• 分子量: 264.324
• InChiKey: JRGDAFHBDNQNDH-VQXHTEKXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  66.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (1R,2S,5S)-3-((S)-2-amino-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate 、 3-[(2S)-2-isocyanato-3,3-dimethylbutyl]-3-azabicyclo[3.2.1]octane-2,4-dione 在 N-甲基吗啉 作用下， 生成
  参考文献：
  名称：

  Potent aza-peptide derived inhibitors of HCV NS3 protease

  摘要：

  Chronic hepatitis C infection is the primary cause for cirrhosis of the liver and hepatocellular carcinoma leading to liver failure and transplantation. The etiological agent hepatitis C virus produces a single positive strand RNA that is processed further with the help of NS3 serine protease to produce mature virus. Inhibition of this protease can potentially be used to develop drugs for HCV infections. Boceprevir is a ketoamide derived novel inhibitor of HCV NS3 protease that has been progressed to clinical trials and proven to be efficacious in humans. Herein, we report our efforts in identifying an aza-peptide derivative as a potential second generation compound, that lacks electrophilic ketoamide group and are potent in enzyme and replicon assay. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.06.060

文献信息

• Discovery and Structure−Activity Relationship of P₁−P₃ Ketoamide Derived Macrocyclic Inhibitors of Hepatitis C Virus NS3 Protease
  作者：Srikanth Venkatraman、Francisco Velazquez、Wanli Wu、Melissa Blackman、Kevin X. Chen、Stephane Bogen、Latha Nair、Xiao Tong、Robert Chase、Andrea Hart、Sony Agrawal、John Pichardo、Andrew Prongay、Kuo-Chi Cheng、Viyyoor Girijavallabhan、John Piwinski、Neng-Yang Shih、F. George Njoroge

  DOI：10.1021/jm800940u

  日期：2009.1.22

  Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, and affects more than 200 million people worldwide. Although combination therapy of interferon-alpha and ribavirin is reasonably successful in treating 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 a series of ketoamide derived P-1-P-3 macrocyclic inhibitors that are more potent than the first generation clinical candidate, boceprevir (1, Sch 503034), is discussed. The optimization of these macrocyclic inhibitors identified a P-3 imide capped analogue 52 that was 20 times more potent than 1 and demonstrated good oral pharmacokinetics in rats. X-ray structure of 52 bound to NS3 protease and biological data are also discussed.
• HYDRAZIDO-PEPTIDES AS INHIBITORS OF HCV NS3-PROTEASE
  申请人：Venkatraman Srikanth

  公开号：US20100104534A1

  公开（公告）日：2010-04-29

  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.
• Macrocyclic Inhibitors of Hepatitis C Virus NS3 Serine Protease
  申请人：Venkatraman Srikanth

  公开号：US20110150835A1

  公开（公告）日：2011-06-23

  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.
• US7592419B2
  申请人：——

  公开号：US7592419B2

  公开（公告）日：2009-09-22
• [EN] HYDRAZIDO-PEPTIDES AS INHIBITORS OF HCV NS3-PROTEASE<br/>[FR] PEPTIDES HYDRAZIDO EN TANT QU'INHIBITEURS DE LA PROTÉASE NS3 DU HCV
  申请人：SCHERING CORP

  公开号：WO2008118332A2

  公开（公告）日：2008-10-02

  [EN] 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.
  [FR] La présente invention concerne de nouveaux composés ayant une activité inhibitrice de la protéase du HCV ainsi que des procédés pour les préparer. Dans un autre mode de réalisation, l'invention décrit des compositions pharmaceutiques comprenant ces composés ainsi que leurs procédés d'utilisation pour traiter les troubles associés à la protéase du HCV.