Methyl 2-diethoxyphosphoryl-3-methylbutanoate | 1310552-15-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Methyl 2-diethoxyphosphoryl-3-methylbutanoate
• 英文别名: methyl 2-diethoxyphosphoryl-3-methylbutanoate
• CAS: 1310552-15-8
• 化学式: C₁₀H₂₁O₅P
• 分子量: 252.247
• InChiKey: QVKLBWYCEQZZGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,4R,5R)-4-(tert-Butyl-dimethyl-silanyloxy)-5-(2-oxo-ethyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 、 Methyl 2-diethoxyphosphoryl-3-methylbutanoate 在 sodium hydride 作用下， 生成 、
  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：

  2-碘代丙烷 、 膦酰基乙酸甲酯二乙酯 在 potassium tert-butylate 作用下， 以 二甲基亚砜 为溶剂， 以62%的产率得到Methyl 2-diethoxyphosphoryl-3-methylbutanoate
  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.