(1SR,2SR,3SR)-1-fluoro-2-(4-(5-methylpyrimidin-2-yl)phenyl)-3-phenylcyclopropanecarboxylic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (1SR,2SR,3SR)-1-fluoro-2-(4-(5-methylpyrimidin-2-yl)phenyl)-3-phenylcyclopropanecarboxylic acid
• 英文别名: (1S*,2S*,3S*)-1-fluoro-2-(4-(5-methylpyrimidin-2-yl)phenyl)-3-phenylcyclopropanecarboxylic acid；(1S*,2S*,3S*)-1-Fluoro-2-(4-(5-methylpyrimidin-2-yl)phenyl)-3-phenylcyclopropanecarboxylic acid；(1S,2S,3S)-1-fluoro-2-[4-(5-methylpyrimidin-2-yl)phenyl]-3-phenylcyclopropane-1-carboxylic acid
• 化学式: C₂₁H₁₇FN₂O₂
• 分子量: 348.377
• InChiKey: BBMNPFBWUHSLIS-OPYAIIAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1SR,2SR,3SR)-1-fluoro-2-(4-(5-methylpyrimidin-2-yl)phenyl)-3-phenylcyclopropanecarboxylic acid 在 吡啶 、 盐酸羟胺 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 反应 2.0h， 生成 (1S,2S,3S)-1-fluoro-N-hydroxy-2-(4-(5-methylpyrimidin-2-yl)phenyl)-3-phenylcyclopropanecarboxamide
  参考文献：
  名称：

  Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class IIa Histone Deacetylase (HDAC) Inhibitors

  摘要：

  Potent and selective class Ha HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class Ha HDAC catalytic site inhibition in preclinical disease models.

  DOI：

  10.1021/acsmedchemlett.5b00302
• 作为产物：
  描述：

  3-(4-溴苯基)-2-丙酸甲酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 12-冠醚-4 、 potassium acetate 、 sodium carbonate 、 lithium hexamethyldisilazane 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 20.5h， 生成 (1SR,2SR,3SR)-1-fluoro-2-(4-(5-methylpyrimidin-2-yl)phenyl)-3-phenylcyclopropanecarboxylic acid
  参考文献：
  名称：

  Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class IIa Histone Deacetylase (HDAC) Inhibitors

  摘要：

  Potent and selective class Ha HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class Ha HDAC catalytic site inhibition in preclinical disease models.

  DOI：

  10.1021/acsmedchemlett.5b00302

文献信息

• HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF
  申请人：CHDI FOUNDATION, INC.

  公开号：US20150203468A1

  公开（公告）日：2015-07-23

  Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use.

  提供了某些式I的组蛋白去乙酰化酶（HDAC）抑制剂，以及它们的组合物和使用方法。
• [EN] HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS D'HISTONE DÉSACÉTYLASE AINSI QUE COMPOSITIONS ET MÉTHODES D'UTILISATION ASSOCIÉES
  申请人：CHDI FOUNDATION INC

  公开号：WO2014014900A8

  公开（公告）日：2014-03-27
• US9505736B2
  申请人：——

  公开号：US9505736B2

  公开（公告）日：2016-11-29
• US9855267B2
  申请人：——

  公开号：US9855267B2

  公开（公告）日：2018-01-02
• Potent, Selective, and CNS-Penetrant Tetrasubstituted Cyclopropane Class IIa Histone Deacetylase (HDAC) Inhibitors
  作者：Christopher A. Luckhurst、Perla Breccia、Andrew J. Stott、Omar Aziz、Helen L. Birch、Roland W. Bürli、Samantha J. Hughes、Rebecca E. Jarvis、Marieke Lamers、Philip M. Leonard、Kim L. Matthews、George McAllister、Scott Pollack、Elizabeth Saville-Stones、Grant Wishart、Dawn Yates、Celia Dominguez

  DOI：10.1021/acsmedchemlett.5b00302

  日期：2016.1.14

  Potent and selective class Ha HDAC tetrasubstituted cyclopropane hydroxamic acid inhibitors were identified with high oral bioavailability that exhibited good brain and muscle exposure. Compound 14 displayed suitable properties for assessment of the impact of class Ha HDAC catalytic site inhibition in preclinical disease models.