(1R,3S,6R,8aR)-1-[7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-5-oxo-6-propan-2-yl-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carboxylic acid | 1310552-22-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (1R,3S,6R,8aR)-1-[7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-5-oxo-6-propan-2-yl-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carboxylic acid
• CAS: 1310552-22-7
• 化学式: C₂₉H₃₅N₃O₅S
• 分子量: 537.68
• InChiKey: QRSVCIMEISXDFL-SQTZCGGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-氨基-N-(环丙基磺酰基)-2-乙烯基-环丙烷羧胺盐酸盐 、 (1R,3S,6R,8aR)-1-[7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-5-oxo-6-propan-2-yl-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carboxylic acid 在 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-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到(1R,3S,6R,8aR)-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-1-[7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-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
• 作为产物：
  描述：

  在 potassium tert-butylate 、 四丁基氟化铵 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 (1R,3S,6R,8aR)-1-[7-methoxy-8-methyl-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-5-oxo-6-propan-2-yl-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carboxylic acid
  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