(5-chloro-2,4-dihydroxy-phenyl)-[1-(pyrrolidine-1-carbonyl)-1,3-dihydroisoindol-2-yl]-methanone | 1023885-06-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (5-chloro-2,4-dihydroxy-phenyl)-[1-(pyrrolidine-1-carbonyl)-1,3-dihydroisoindol-2-yl]-methanone
• 英文别名: 4-chloro-6-((1-(pyrrolidin-1-ylcarbonyl)-1,3-dihydro-2H-isoindol-2-yl)carbonyl)benzene-1,3-diol；[2-(5-Chloro-2,4-dihydroxybenzoyl)-1,3-dihydroisoindol-1-yl]-pyrrolidin-1-ylmethanone
• CAS: 1023885-06-4
• 化学式: C₂₀H₁₉ClN₂O₄
• 分子量: 386.835
• InChiKey: OMUNXMLDEXCDQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5-chloro-2,4-dihydroxy-phenyl)-[1-(pyrrolidine-1-carbonyl)-1,3-dihydroisoindol-2-yl]-methanone 在 Chiralcel OJ-H SFC column 作用下， 以 甲醇 、 二氧化碳 为溶剂， 生成 (S)-(5-chloro-2,4-dihydroxy-phenyl)-[1-(pyrrolidine-1-carbonyl)-1,3-dihydroisoindol-2-yl]-methanone 、 (R)-(5-chloro-2,4-dihydroxy-phenyl)-[1-(pyrrolidine-1-carbonyl)-1,3-dihydroisoindol-2-yl]-methanone
  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
• 作为产物：
  描述：

  [2-[5-Chloro-2,4-bis(methoxymethoxy)benzoyl]-1,3-dihydroisoindol-1-yl]-pyrrolidin-1-ylmethanone 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 (5-chloro-2,4-dihydroxy-phenyl)-[1-(pyrrolidine-1-carbonyl)-1,3-dihydroisoindol-2-yl]-methanone
  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：——
• [EN] AMIDE RESORCINOL COMPOUNDS<br/>[FR] COMPOSÉS D'AMIDE RÉSORCINOL
  申请人：PFIZER PROD INC

  公开号：WO2008053319A1

  公开（公告）日：2008-05-08

  [EN] The present invention is directed to amide resorcinol compounds and pharmaceutically acceptable salts and solvates thereof, their synthesis, and their use as HSP-90 inhibitors.
  [FR] La présente invention concerne des composés d'amide résorcinol et leurs sels et solvates pharmaceutiquement acceptables, leur synthèse et leur utilisation en tant qu'inhibiteurs de HSP-90.