3-(2-(S)-cyclohexyl-2-isobutoxycarbonylaminoacetyl)-1-(R),5-(S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-(S)-carboxylic acid | 394734-86-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-(2-(S)-cyclohexyl-2-isobutoxycarbonylaminoacetyl)-1-(R),5-(S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-(S)-carboxylic acid
• 英文别名: (1R,2S,5S)-3-[(2S)-2-cyclohexyl-2-(2-methylpropoxycarbonylamino)acetyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylic acid
• CAS: 394734-86-2
• 化学式: C₂₁H₃₄N₂O₅
• 分子量: 394.511
• InChiKey: LYIBACKJRPNVGG-QAETUUGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2-(S)-cyclohexyl-2-isobutoxycarbonylaminoacetyl)-1-(R),5-(S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-(S)-carboxylic acid 在 戴斯-马丁氧化剂 、 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 二氯甲烷 为溶剂， 生成 2-methylpropyl N-[(1S)-1-cyclohexyl-2-[(1R,2S,5S)-2-({1-[({[(S)-(dimethylcarbamoyl)(phenyl)methyl]carbamoyl}methyl)carbamoyl]-1-oxopentan-2-yl}carbamoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-2-oxoethyl]carbamate
  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
• 作为产物：
  描述：

  (S)-cyclohexyl-isobutoxycarbonylamino-acetic acid 在 chromium(VI) oxide 、 硫酸 、 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 乙腈 为溶剂， 反应 3.0h， 生成 3-(2-(S)-cyclohexyl-2-isobutoxycarbonylaminoacetyl)-1-(R),5-(S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-(S)-carboxylic acid
  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

• Discovery of SCH446211 (SCH6):  A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication
  作者：Stéphane L. Bogen、Ashok Arasappan、Frank Bennett、Kevin Chen、Edwin Jao、Yi-Tsung Liu、Raymond G. Lovey、Srikanth Venkatraman、Weidong Pan、Tajel Parekh、Russel E. Pike、Sumei Ruan、Rong Liu、Bahige Baroudy、Sony Agrawal、Robert Chase、Paul Ingravallo、John Pichardo、Andrew Prongay、Jean-Marc Brisson、Tony Y. Hsieh、Kuo-Chi Cheng、Scott J. Kemp、Odile E. Levy、Marguerita Lim-Wilby、Susan Y. Tamura、Anil K. Saksena、Viyyoor Girijavallabhan、F. George Njoroge

  DOI：10.1021/jm060077j

  日期：2006.5.1

  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.