tert-butyl N-[(1S)-1-[(1S,4S,5R)-4-[1-[2-(allylamino)-2-oxo-acetyl]butylcarbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]carbamate | 865454-42-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: tert-butyl N-[(1S)-1-[(1S,4S,5R)-4-[1-[2-(allylamino)-2-oxo-acetyl]butylcarbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]carbamate
• 英文别名: tert-butyl N-[(2S)-1-[(1R,2S,5S)-2-[[1,2-dioxo-1-(prop-2-enylamino)hexan-3-yl]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate
• CAS: 865454-42-8
• 化学式: C₂₈H₄₆N₄O₆
• 分子量: 534.696
• InChiKey: CGGQLYZSUVRIDT-QWYSVXDISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  134
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(1S)-1-[(1S,4S,5R)-4-[1-[2-(allylamino)-2-oxo-acetyl]butylcarbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]carbamate 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 (1R,2S,5S)-3-[(2S)-2-amino-3,3-dimethylbutanoyl]-N-[1,2-dioxo-1-(prop-2-enylamino)hexan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide;hydrochloride
  参考文献：
  名称：

  Toward the Back-Up of Boceprevir (SCH 503034): Discovery of New Extended P₄-Capped Ketoamide Inhibitors of Hepatitis C Virus NS3 Serine Protease with Improved Potency and Pharmacokinetic Profiles

  摘要：

  Hepatitis C is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically an estimated 300 million people worldwide. Results of Phase I clinical studies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) were encouraging, and thus, additional human clinical studies are underway. 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 and optimization of the P-1' capping led to the discovery of new ketoamide inhibitors of the HCV NS3 serine protease with improved in vitro potency. In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P-4-capped inhibitors were also found to have improved PK profile.

  DOI：

  10.1021/jm801632a
• 作为产物：
  描述：

  tert-butyl N-[(2S)-1-[(1R,2S,5S)-2-[[2-hydroxy-1-oxo-1-(prop-2-enylamino)hexan-3-yl]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate 在 戴斯-马丁氧化剂 作用下， 生成 tert-butyl N-[(1S)-1-[(1S,4S,5R)-4-[1-[2-(allylamino)-2-oxo-acetyl]butylcarbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]carbamate
  参考文献：
  名称：

  Toward the Back-Up of Boceprevir (SCH 503034): Discovery of New Extended P₄-Capped Ketoamide Inhibitors of Hepatitis C Virus NS3 Serine Protease with Improved Potency and Pharmacokinetic Profiles

  摘要：

  Hepatitis C is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically an estimated 300 million people worldwide. Results of Phase I clinical studies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) were encouraging, and thus, additional human clinical studies are underway. 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 and optimization of the P-1' capping led to the discovery of new ketoamide inhibitors of the HCV NS3 serine protease with improved in vitro potency. In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P-4-capped inhibitors were also found to have improved PK profile.

  DOI：

  10.1021/jm801632a

文献信息

• [EN] COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE<br/>[FR] NOUVEAUX COMPOSES EN TANT QU'INHIBITEURS DE LA PROTEASE SERINE NS3 DU VIRUS DE L'HEPATITE C
  申请人：SCHERING CORP

  公开号：WO2005087721A3

  公开（公告）日：2005-11-10
• Novel compounds as inhibitors of hepatitis C virus NS3 serine protease
  申请人：Venkatraman Srikanth

  公开号：US20070032434A1

  公开（公告）日：2007-02-08

  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.
• US7192957B2
  申请人：——

  公开号：US7192957B2

  公开（公告）日：2007-03-20
• US7718691B2
  申请人：——

  公开号：US7718691B2

  公开（公告）日：2010-05-18
• US7759499B2
  申请人：——

  公开号：US7759499B2

  公开（公告）日：2010-07-20