(1R,3S,6R,8aR)-1-[8-chloro-7-(2-methoxyethoxy)-2-(6-propan-2-ylpyridin-2-yl)quinolin-4-yl]oxy-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-5-oxo-6-propan-2-yl-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carboxamide | 1310551-33-7

• 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: (1R,3S,6R,8aR)-1-[8-chloro-7-(2-methoxyethoxy)-2-(6-propan-2-ylpyridin-2-yl)quinolin-4-yl]oxy-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-5-oxo-6-propan-2-yl-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carboxamide
• CAS: 1310551-33-7
• 化学式: C₄₁H₅₀ClN₅O₈S
• 分子量: 808.396
• InChiKey: XBCMFBIEQDRBOJ-MPQXONFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  56
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  175
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 potassium tert-butylate 、 四丁基氟化铵 、 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1R,3S,6R,8aR)-1-[8-chloro-7-(2-methoxyethoxy)-2-(6-propan-2-ylpyridin-2-yl)quinolin-4-yl]oxy-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-5-oxo-6-propan-2-yl-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carboxamide
  参考文献：
  名称：

  Novel, potent and orally bioavailable indolizidinone-derived inhibitors of the hepatitis C virus NS3 protease

  摘要：

  A novel, potent, and orally bioavailable class of product-like inhibitors of the HCV NS3 protease was discovered by constraining the P2-P3 amide bond and the P3 hydrocarbon substituent to the proteasebound conformation. This preorganization was accomplished by incorporation of the P2-P3 amide into a six-membered ring attached to the P2-proline 5-position. isothermal calorimetric characterization of the role of hydrocarbon substitution of this six-membered ring, upon binding the HCV NS3 protease, was found to be exclusively entropic in nature. The synthesis, preliminary SAR and pharmacokinetic profiling of this compact, indolizidinone-derived scaffold are described. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.107

文献信息

• ANTIVIRAL COMPOUNDS
  申请人：Cai Zhenhong R.

  公开号：US20110135599A1

  公开（公告）日：2011-06-09

  The present application includes novel inhibitors of HCV, compositions containing such compounds, therapeutic methods that include the administration of such compounds.

  本申请包括HCV的新型抑制剂，含有这些化合物的组合物，以及包括这些化合物的给药的治疗方法。
• US8927484B2
  申请人：——

  公开号：US8927484B2

  公开（公告）日：2015-01-06
• Novel, potent and orally bioavailable indolizidinone-derived inhibitors of the hepatitis C virus NS3 protease
  作者：Michael O. Clarke、Daniel Byun、Xiaowu Chen、Edward Doerffler、Stephanie A. Leavitt、X. Christopher Sheng、Cheng Y. Yang、Choung U. Kim

  DOI：10.1016/j.bmcl.2011.11.107

  日期：2012.1

  A novel, potent, and orally bioavailable class of product-like inhibitors of the HCV NS3 protease was discovered by constraining the P2-P3 amide bond and the P3 hydrocarbon substituent to the proteasebound conformation. This preorganization was accomplished by incorporation of the P2-P3 amide into a six-membered ring attached to the P2-proline 5-position. isothermal calorimetric characterization of the role of hydrocarbon substitution of this six-membered ring, upon binding the HCV NS3 protease, was found to be exclusively entropic in nature. The synthesis, preliminary SAR and pharmacokinetic profiling of this compact, indolizidinone-derived scaffold are described. (C) 2011 Elsevier Ltd. All rights reserved.