2-[(1-Isocyanatocyclohexyl)methyl]thiophene | 864801-79-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: 2-[(1-Isocyanatocyclohexyl)methyl]thiophene
• CAS: 864801-79-6
• 化学式: C₁₂H₁₅NOS
• 分子量: 221.323
• InChiKey: QMQJAIFXQIWMJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,2S,5S)-N-(4-amino-1-cyclopropyl-3,4-dioxobutan-2-yl)-3-((2S)-2-(3-(1-(((benzyloxy)methoxy)(phenyl)methyl)cyclopentyl)ureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide 、 2-[(1-Isocyanatocyclohexyl)methyl]thiophene 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir®: A change in direction in the search for a second generation HCV NS3 protease inhibitor

  摘要：

  In the search for a second generation HCV protease inhibitor, molecular modeling studies of the X-ray crystal structure of Boceprevir (R) 1 bound to the NS3 protein suggest that expansion into the S4 pocket could provide additional hydrophobic Van der Waals interactions. Effective replacement of the P4 tertbutyl with a cyclohexylmethyl ligand led to inhibitor 2 with improved enzyme and replicon activities. Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.063
• 作为产物：
  描述：

  1-(2-Thenyl)-cyclohexancarbonsaeure 在 二苯基膦叠氮化物 、 三乙胺 作用下， 以 甲苯 为溶剂， 生成 2-[(1-Isocyanatocyclohexyl)methyl]thiophene
  参考文献：
  名称：

  The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir®: A change in direction in the search for a second generation HCV NS3 protease inhibitor

  摘要：

  In the search for a second generation HCV protease inhibitor, molecular modeling studies of the X-ray crystal structure of Boceprevir (R) 1 bound to the NS3 protein suggest that expansion into the S4 pocket could provide additional hydrophobic Van der Waals interactions. Effective replacement of the P4 tertbutyl with a cyclohexylmethyl ligand led to inhibitor 2 with improved enzyme and replicon activities. Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.063

文献信息

• Novel inhibitors of Hepatitis C virus NS3 protease
  申请人：Bogen L. Stephane

  公开号：US20070142301A1

  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.
• US7205330B2
  申请人：——

  公开号：US7205330B2

  公开（公告）日：2007-04-17
• US7423058B2
  申请人：——

  公开号：US7423058B2

  公开（公告）日：2008-09-09
• The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir®: A change in direction in the search for a second generation HCV NS3 protease inhibitor
  作者：Frank Bennett、Yuhua Huang、Siska Hendrata、Raymond Lovey、Stephane L. Bogen、Weidong Pan、Zhuyan Guo、Andrew Prongay、Kevin X. Chen、Ashok Arasappan、Srikanth Venkatraman、Francisco Velazquez、Latha Nair、Mousumi Sannigrahi、Xiao Tong、John Pichardo、Kuo-Chi Cheng、Viyyoor M. Girijavallabhan、Anil K. Saksena、F. George Njoroge

  DOI：10.1016/j.bmcl.2010.02.063

  日期：2010.4

  In the search for a second generation HCV protease inhibitor, molecular modeling studies of the X-ray crystal structure of Boceprevir (R) 1 bound to the NS3 protein suggest that expansion into the S4 pocket could provide additional hydrophobic Van der Waals interactions. Effective replacement of the P4 tertbutyl with a cyclohexylmethyl ligand led to inhibitor 2 with improved enzyme and replicon activities. Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration. (C) 2010 Elsevier Ltd. All rights reserved.