(1S,2S)-N-hydroxy-2-phenylcyclopropanecarboxamide | 1512872-16-0

• 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: (1S,2S)-N-hydroxy-2-phenylcyclopropanecarboxamide
• 英文别名: (2S,3S)-N-hydroxy-2,3-methano-3-phenylpropanamide；(1S,2S)-N-hydroxy-2-phenylcyclopropane-1-carboxamide
• CAS: 1512872-16-0
• 化学式: C₁₀H₁₁NO₂
• 分子量: 177.203
• InChiKey: QCZUQSWZNXVMLT-BDAKNGLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1S,2S)-N-hydroxy-2-phenylcyclopropanecarboxamide 、 苯甲醇 在 N,N-二异丙基乙胺 、 对硝基苯磺酰氯 、 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 以87%的产率得到(1S,2R)-(+)-N-Cbz-tranylcypromine
  参考文献：
  名称：

  Amidation of carboxylic acids via the mixed carbonic carboxylic anhydrides and its application to synthesis of antidepressant (1 S ,2 R )-tranylcypromine

  摘要：

  Primary amidations of carboxylic acids 1 or 3 with NH4Cl in the presence of ClCO2Et and Et3N were developed to afford the corresponding primary amides in 22% to quantitative yields. Additionally, we have applied the amidation to the preparation of various amides containing hydroxamic acids and achieved the synthesis of (1S,2R)-tranylcypromine as an antidepressant medicine via Lossen rearrangement. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2017.10.015
• 作为产物：
  描述：

  (1S,2S)-2-phenylcyclopropane-1-carboxylic acid 在 氯甲酸乙酯 、 三乙胺 、 盐酸羟胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.17h， 以82%的产率得到(1S,2S)-N-hydroxy-2-phenylcyclopropanecarboxamide
  参考文献：
  名称：

  Amidation of carboxylic acids via the mixed carbonic carboxylic anhydrides and its application to synthesis of antidepressant (1 S ,2 R )-tranylcypromine

  摘要：

  Primary amidations of carboxylic acids 1 or 3 with NH4Cl in the presence of ClCO2Et and Et3N were developed to afford the corresponding primary amides in 22% to quantitative yields. Additionally, we have applied the amidation to the preparation of various amides containing hydroxamic acids and achieved the synthesis of (1S,2R)-tranylcypromine as an antidepressant medicine via Lossen rearrangement. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2017.10.015

文献信息

• Design, Synthesis, and Biological Evaluation of Potent and Selective Class IIa Histone Deacetylase (HDAC) Inhibitors as a Potential Therapy for Huntington’s Disease
  作者：Roland W. Bürli、Christopher A. Luckhurst、Omar Aziz、Kim L. Matthews、Dawn Yates、Kathy. A. Lyons、Maria Beconi、George McAllister、Perla Breccia、Andrew J. Stott、Stephen D. Penrose、Michael Wall、Marieke Lamers、Philip Leonard、Ilka Müller、Christine M. Richardson、Rebecca Jarvis、Liz Stones、Samantha Hughes、Grant Wishart、Alan F. Haughan、Catherine O’Connell、Tania Mead、Hannah McNeil、Julie Vann、John Mangette、Michel Maillard、Vahri Beaumont、Ignacio Munoz-Sanjuan、Celia Dominguez

  DOI：10.1021/jm4011884

  日期：2013.12.27

  Inhibition of class IIa histone deacetylase (HDAC) enzymes have been suggested as a therapeutic strategy for a number of diseases, including Huntington’s disease. Catalytic-site small molecule inhibitors of the class IIa HDAC4, -5, -7, and -9 were developed. These trisubstituted diarylcyclopropanehydroxamic acids were designed to exploit a lower pocket that is characteristic for the class IIa HDACs

  有人提出抑制IIa类组蛋白脱乙酰基酶（HDAC）酶可以作为许多疾病的治疗策略，包括亨廷顿氏病。开发了IIa类HDAC4，-5，-7和-9的催化位点小分子抑制剂。这些三取代的二芳基环丙烷异羟肟酸被设计用于开发IIa类HDAC特有的下部口袋，而其他HDAC类中不存在。所选的抑制剂与人HDAC4的催化结构域共结晶。我们以“闭环”形式描述了第一个HDAC4催化域晶体结构，在我们看来代表了生物学相关的构象。我们已经证明这些分子可以区分IIa类HDAC与I类和IIb类亚型。它们表现出药代动力学特性，应该能够评估它们在周围和中枢神经系统疾病中的治疗效果。这些选择性抑制剂提供了用于评估体内临床前模型中潜在功效的手段。