2-[5-chloro-2,4-bis(methoxymethoxy)benzoyl]-N,N-dimethyl-1,3-dihydroisoindole-1-carboxamide | 1029650-02-9

• 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: 2-[5-chloro-2,4-bis(methoxymethoxy)benzoyl]-N,N-dimethyl-1,3-dihydroisoindole-1-carboxamide
• CAS: 1029650-02-9
• 化学式: C₂₂H₂₅ClN₂O₆
• 分子量: 448.903
• InChiKey: YCCGNEFIENBZTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  77.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[5-chloro-2,4-bis(methoxymethoxy)benzoyl]-N,N-dimethyl-1,3-dihydroisoindole-1-carboxamide 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 2-(5-chloro-2,4-dihydroxy-benzoyl)-2,3-dihydro-1H-isoindole-1-carboxylic acid dimethylamide
  参考文献：
  名称：

  WO2008/53319

  摘要：

  公开号：
• 作为产物：
  描述：

  2-(5-chloro-2,4-bis-methoxymethoxybenzoyl)-2,3-dihydro-1H-isoindole-1-carboxylic acid 、 二甲胺 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2-[5-chloro-2,4-bis(methoxymethoxy)benzoyl]-N,N-dimethyl-1,3-dihydroisoindole-1-carboxamide
  参考文献：
  名称：

  Dihydroxyphenylisoindoline Amides as Orally Bioavailable Inhibitors of the Heat Shock Protein 90 (Hsp90) Molecular Chaperone

  摘要：

  The discovery and optimization of potency and metabolic stability of a novel class of dihyroxyphenylisoindoline amides as Hsp90 inhibitors are presented. Optimization of a screening hit using structure-based design and modification of log D and chemical structural features led to the identification of a class of orally bioavailable non-quinone-containing Hsp90 inhibitors. This class is exemplified by 14 and 15, which possess improved cell potency and pharmacokinetic profiles compared with the original screening hit.

  DOI：

  10.1021/jm901209q

文献信息

• WO2008/53319
  申请人：——

  公开号：——

  公开（公告）日：——
• Dihydroxyphenylisoindoline Amides as Orally Bioavailable Inhibitors of the Heat Shock Protein 90 (Hsp90) Molecular Chaperone
  作者：Pei-Pei Kung、Buwen Huang、Gang Zhang、Joe Zhongxiang Zhou、Jeff Wang、Jennifer A. Digits、Judith Skaptason、Shinji Yamazaki、David Neul、Michael Zientek、Jeff Elleraas、Pramod Mehta、Min-Jean Yin、Michael J. Hickey、Ketan S. Gajiwala、Caroline Rodgers、Jay F. Davies、Michael R. Gehring

  DOI：10.1021/jm901209q

  日期：2010.1.14

  The discovery and optimization of potency and metabolic stability of a novel class of dihyroxyphenylisoindoline amides as Hsp90 inhibitors are presented. Optimization of a screening hit using structure-based design and modification of log D and chemical structural features led to the identification of a class of orally bioavailable non-quinone-containing Hsp90 inhibitors. This class is exemplified by 14 and 15, which possess improved cell potency and pharmacokinetic profiles compared with the original screening hit.