{1-[({[((S)-Dimethylcarbamoyl-phenyl-methyl)-carbamoyl]-methyl}-carbamoyl)-hydroxy-methyl]-pentyl}-carbamic acid tert-butyl ester | 367258-50-2

• 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: {1-[({[((S)-Dimethylcarbamoyl-phenyl-methyl)-carbamoyl]-methyl}-carbamoyl)-hydroxy-methyl]-pentyl}-carbamic acid tert-butyl ester
• 英文别名: Boc-bAla(2-OH,3-Bu)-Gly-Phg-NMe2；tert-butyl N-[1-[[2-[[(1S)-2-(dimethylamino)-2-oxo-1-phenylethyl]amino]-2-oxoethyl]amino]-2-hydroxy-1-oxoheptan-3-yl]carbamate
• CAS: 367258-50-2
• 化学式: C₂₄H₃₈N₄O₆
• 分子量: 478.589
• InChiKey: FCADATXPWMAQLE-SYYJFZTOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  137
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  {1-[({[((S)-Dimethylcarbamoyl-phenyl-methyl)-carbamoyl]-methyl}-carbamoyl)-hydroxy-methyl]-pentyl}-carbamic acid tert-butyl ester 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Novel inhibitors of hepatitis C NS3–NS4A serine protease derived from 2-aza-bicyclo[2.2.1]heptane-3-carboxylic acid

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2005.12.046
• 作为产物：
  描述：

  1-硝基戊烷 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 20.0 ℃ 、413.68 kPa 条件下， 反应 18.0h， 生成 {1-[({[((S)-Dimethylcarbamoyl-phenyl-methyl)-carbamoyl]-methyl}-carbamoyl)-hydroxy-methyl]-pentyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of SCH446211 (SCH6):  A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication

  摘要：

  Introduction of various modified prolines at P-2 and optimization of the P-1 side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K-i* = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC50 and IC90 of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.

  DOI：

  10.1021/jm060077j

文献信息

• Proline-Based Macrocyclic Inhibitors of the Hepatitis C Virus: Stereoselective Synthesis and Biological Activity
  作者：Kevin X. Chen、F. George Njoroge、Bancha Vibulbhan、Andrew Prongay、John Pichardo、Vincent Madison、Alexei Buevich、Tze-Ming Chan

  DOI：10.1002/anie.200501553

  日期：2005.11.4