(1R,5S)-3-[2(S)-[[[[1(S)-[(4,4-dimethyl-2,6-dioxo-1-piperidinyl)-methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-N-[1-[1,2-dioxo-2-(propylamino)ethyl]-pentyl]-6,6-dimethyl-3-azabicyclo-[3.1.0]hexane-2(S)-carboxamide | 864947-76-2

• 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: (1R,5S)-3-[2(S)-[[[[1(S)-[(4,4-dimethyl-2,6-dioxo-1-piperidinyl)-methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-N-[1-[1,2-dioxo-2-(propylamino)ethyl]-pentyl]-6,6-dimethyl-3-azabicyclo-[3.1.0]hexane-2(S)-carboxamide
• 英文别名: (1R,2S,5S)-3-[(2S)-2-[[(2S)-1-(4,4-dimethyl-2,6-dioxopiperidin-1-yl)-3,3-dimethylbutan-2-yl]carbamoylamino]-3,3-dimethylbutanoyl]-N-[1,2-dioxo-1-(propylamino)heptan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
• CAS: 864947-76-2
• 化学式: C₃₈H₆₄N₆O₇
• 分子量: 716.962
• InChiKey: ZCNJNFHBYZGZRB-ZFGQAXDQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  在 戴斯-马丁氧化剂 作用下， 生成 (1R,5S)-3-[2(S)-[[[[1(S)-[(4,4-dimethyl-2,6-dioxo-1-piperidinyl)-methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-N-[1-[1,2-dioxo-2-(propylamino)ethyl]-pentyl]-6,6-dimethyl-3-azabicyclo-[3.1.0]hexane-2(S)-carboxamide
  参考文献：
  名称：

  Second-Generation Highly Potent and Selective Inhibitors of the Hepatitis C Virus NS3 Serine Protease

  摘要：

  The hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The moderate efficacy along with side effects of the current pegylated interferon and ribavirin combination therapy underscores the need for more effective and safer new treatment. In an effort to improve upon our current clinical candidate, Boceprevir (SCH 503034), extensive SAR studies were performed on the P3 capping moieties. This led to the discovery of tert-leucinol derived cyclic imides as a potent series of novel P3 capping groups. Thus, the introduction of these imide caps improved the cell-based replicon EC90 by more than 10-fold. A number of imides with various substitutions, ring sizes, bicyclic systems, and heterocyclic rings were explored. The 4,4-dimethyl substituted glutarimide emerged as the best cap as exemplified in compound 21 (K-i* = 4 nM, EC90 = 40 nM). Systematic optimization of different positions (P', P3, and P1) of the inhibitor resulted in the identification of the lead compound 46, which had an excellent potency (K-i* = 4 nM, EC90 = 30 nM) and good pharmacokinetic profile (22% and 35% bioavailability in rats and dogs, respectively). X-ray structure of inhibitor 46 bound to the enzyme revealed that there was an additional hydrogen bonding interaction between one of the imide carbonyls and Cys159.

  DOI：

  10.1021/jm801238q

文献信息

• Pharmaceutical formulations and methods of treatment using the same
  申请人：Malcolm A. Bruce

  公开号：US20070010431A1

  公开（公告）日：2007-01-11

  Pharmaceutical formulations containing at least one compound of Formulae I-XXVI herein and at least one surfactant. Pharmaceutically acceptable carriers and excipients may also be included in the formulations. The formulations of the present invention are suited for use in single unit dosages.

  含有本文中的至少一种I-XXVI式化合物和至少一种表面活性剂的制药配方。 制剂中还可以包括药用可接受的载体和辅料。 本发明的制剂适用于单剂量使用。
• Method of treating interferon non-responders using HCV protease inhibitor
  申请人：Albrecht K. Janice

  公开号：US20070004635A1

  公开（公告）日：2007-01-04

  A method of treating, preventing or ameliorating one or more symptoms associated with hepatitis C virus (HCV) in a patient in whom either the HCV is of Genotype 1 and/or the patient was previously treated with interferon and the previous interferon therapy was ineffective to treat the one or more symptoms associated with HCV, comprising administering to such a patient an effective amount of at least one compound of formulae I-XXVI of which the following structural formula is exemplary or a pharmaceutically acceptable salt, solvate or ester thereof. Optional combined administration of said at least one compound with an interferon or pegylated interferon and/or ribaviron is also contemplated.
• Novel ketoamides with cyclic P4's as inhibitors of NS3 serine protease of hepatitis C virus
  申请人：Chen X. Kevin

  公开号：US20070093430A1

  公开（公告）日：2007-04-26

  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.
• US7173057B2
  申请人：——

  公开号：US7173057B2

  公开（公告）日：2007-02-06
• US7619094B2
  申请人：——

  公开号：US7619094B2

  公开（公告）日：2009-11-17