4-chloro-6-((3-(4-((3,3-difluoroazetidin-1-yl)carbonyl)-2-methylphenyl)pyrrolidin-1-yl)carbonyl)benzene-1,3-diol | 1023885-07-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 4-chloro-6-((3-(4-((3,3-difluoroazetidin-1-yl)carbonyl)-2-methylphenyl)pyrrolidin-1-yl)carbonyl)benzene-1,3-diol
• 英文别名: [4-[1-(5-Chloro-2,4-dihydroxybenzoyl)pyrrolidin-2-yl]-3-methylphenyl]-(3,3-difluoroazetidin-1-yl)methanone
• CAS: 1023885-07-5
• 化学式: C₂₂H₂₁ClF₂N₂O₄
• 分子量: 450.87
• InChiKey: QUODKSAJAYXMND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-chloro-6-((3-(4-((3,3-difluoroazetidin-1-yl)carbonyl)-2-methylphenyl)pyrrolidin-1-yl)carbonyl)benzene-1,3-diol 生成 [4-[(2R)-1-(5-chloro-2,4-dihydroxybenzoyl)pyrrolidin-2-yl]-3-methylphenyl]-(3,3-difluoroazetidin-1-yl)methanone 、 [4-[(2S)-1-(5-chloro-2,4-dihydroxybenzoyl)pyrrolidin-2-yl]-3-methylphenyl]-(3,3-difluoroazetidin-1-yl)methanone
  参考文献：
  名称：

  Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone

  摘要：

  Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a Hsp90 competitive binding assay. A class of novel and potent small molecule Hsp90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human cancer cell lines in vitro, with IC(50) values averaging 20 nM.

  DOI：

  10.1016/j.bmcl.2008.09.081
• 作为产物：
  描述：

  (4-(1-(5-chloro-2,4-bis(methoxymethoxy)benzoyl)pyrrolidin-2-yl)-3-methylphenyl)(3,3-difluoroazetidin-1-yl)methanone 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 12.0h， 以82%的产率得到4-chloro-6-((3-(4-((3,3-difluoroazetidin-1-yl)carbonyl)-2-methylphenyl)pyrrolidin-1-yl)carbonyl)benzene-1,3-diol
  参考文献：
  名称：

  Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone

  摘要：

  Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a Hsp90 competitive binding assay. A class of novel and potent small molecule Hsp90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human cancer cell lines in vitro, with IC(50) values averaging 20 nM.

  DOI：

  10.1016/j.bmcl.2008.09.081

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.
• Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone
  作者：Pei-Pei Kung、Lee Funk、Jerry Meng、Michael Collins、Joe Zhongxiang Zhou、M. Catherine Johnson、Anne Ekker、Jeff Wang、Pramod Mehta、Min-Jean Yin、Caroline Rodgers、Jay F. Davies、Eileen Bayman、Tod Smeal、Karen A. Maegley、Michael R. Gehring

  DOI：10.1016/j.bmcl.2008.09.081

  日期：2008.12

  Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a Hsp90 competitive binding assay. A class of novel and potent small molecule Hsp90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human cancer cell lines in vitro, with IC(50) values averaging 20 nM.