(R)-1-(5-chloro-2,4-dihydroxy-benzoyl)-pyrrolidine-2-carboxylic acid cyclohexylamide | 1023885-47-3

• 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: (R)-1-(5-chloro-2,4-dihydroxy-benzoyl)-pyrrolidine-2-carboxylic acid cyclohexylamide
• 英文别名: 1-(5-chloro-2,4-dihydroxybenzoyl)-N-cyclohexyl-D-prolinamide；(2R)-1-(5-chloro-2,4-dihydroxybenzoyl)-N-cyclohexylpyrrolidine-2-carboxamide
• CAS: 1023885-47-3
• 化学式: C₁₈H₂₃ClN₂O₄
• 分子量: 366.845
• InChiKey: UAYPYQFHJWZHQA-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  89.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以48.3 mg的产率得到(R)-1-(5-chloro-2,4-dihydroxy-benzoyl)-pyrrolidine-2-carboxylic acid cyclohexylamide
  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

• 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.