2(S)-[[[[2-[(1R,5S)-2(S)-[[[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]amino]carbonyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hex-3-yl]-1(S)-(2,3-dihydro-1H-inden-2-yl)-2-oxoethyl]amino]carbonyl]amino]-3,3-dimethylbutyl dimethylcarbamate | 864825-70-7

• 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: 2(S)-[[[[2-[(1R,5S)-2(S)-[[[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]amino]carbonyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hex-3-yl]-1(S)-(2,3-dihydro-1H-inden-2-yl)-2-oxoethyl]amino]carbonyl]amino]-3,3-dimethylbutyl dimethylcarbamate
• 英文别名: [(2S)-2-[[(1S)-2-[(1S,4S,5R)-4-[[3-amino-1-(cyclobutylmethyl)-2,3-dioxo-propyl]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-1-indan-2-yl-2-oxo-ethyl]carbamoylamino]-3,3-dimethyl-butyl] N,N-dimethylcarbamate；[(2S)-2-[[(1S)-2-[(1R,2S,5S)-2-[(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-1-(2,3-dihydro-1H-inden-2-yl)-2-oxoethyl]carbamoylamino]-3,3-dimethylbutyl] N,N-dimethylcarbamate
• CAS: 864825-70-7
• 化学式: C₃₇H₅₄N₆O₇
• 分子量: 694.872
• InChiKey: IFEFKIFYFPWTGJ-CFZNNNMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  50
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  180
• 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， 以 二氯甲烷 为溶剂， 生成 2(S)-[[[[2-[(1R,5S)-2(S)-[[[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]amino]carbonyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hex-3-yl]-1(S)-(2,3-dihydro-1H-inden-2-yl)-2-oxoethyl]amino]carbonyl]amino]-3,3-dimethylbutyl dimethylcarbamate
  参考文献：
  名称：

  Toward Second Generation Hepatitis C Virus NS3 Serine Protease Inhibitors: Discovery of Novel P4 Modified Analogues with Improved Potency and Pharmacokinetic Profile

  摘要：

  Hepatitis C virus (HCV) infection is a global health crisis leading to liver cirrhosis, hepatocellular carcinoma, and liver failure in humans. Recently, we disclosed the discovery of Boceprevir, SCH 503034 (1), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that is currently undergoing phase III clinical trials. Our efforts toward a second generation HCV NS3 serine protease inhibitor were directed at improving the overall profile of the inhibitor. This article will elaborate on our studies leading to the discovery of new P4 modified inhibitors with enhanced potency and improved oral bioavailability. Thus, introduction of ether and carbamate-derived P4 moieties resulted in improving the replicon potency significantly. Incorporation of the P' secondary amide residue afforded significant improvement in pharmacokinetic properties. Combining the preferred moieties, identified from comprehensive SAR studies, resulted in inhibitors that displayed superior potency and very good oral as well as target organ exposure in rats.

  DOI：

  10.1021/jm801616e

文献信息

• Novel compounds as inhibitors of hepatitis C virus NS3 serine protease
  申请人：Arasappan Ashok

  公开号：US20070142300A1

  公开（公告）日：2007-06-21

  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.
• US7186747B2
  申请人：——

  公开号：US7186747B2

  公开（公告）日：2007-03-06
• US7425576B2
  申请人：——

  公开号：US7425576B2

  公开（公告）日：2008-09-16
• Toward Second Generation Hepatitis C Virus NS3 Serine Protease Inhibitors: Discovery of Novel P4 Modified Analogues with Improved Potency and Pharmacokinetic Profile
  作者：Ashok Arasappan、Angela I. Padilla、Edwin Jao、Frank Bennett、Stephane L. Bogen、Kevin X. Chen、Russell E. Pike、Mousumi Sannigrahi、Joana Soares、Srikanth Venkatraman、Bancha Vibulbhan、Anil K. Saksena、Viyyoor Girijavallabhan、Xiao Tong、Kuo-Chi Cheng、F. George Njoroge

  DOI：10.1021/jm801616e

  日期：2009.5.14

  Hepatitis C virus (HCV) infection is a global health crisis leading to liver cirrhosis, hepatocellular carcinoma, and liver failure in humans. Recently, we disclosed the discovery of Boceprevir, SCH 503034 (1), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that is currently undergoing phase III clinical trials. Our efforts toward a second generation HCV NS3 serine protease inhibitor were directed at improving the overall profile of the inhibitor. This article will elaborate on our studies leading to the discovery of new P4 modified inhibitors with enhanced potency and improved oral bioavailability. Thus, introduction of ether and carbamate-derived P4 moieties resulted in improving the replicon potency significantly. Incorporation of the P' secondary amide residue afforded significant improvement in pharmacokinetic properties. Combining the preferred moieties, identified from comprehensive SAR studies, resulted in inhibitors that displayed superior potency and very good oral as well as target organ exposure in rats.