5-[1-(3-phenyl-propyl)-1H-pyrazol-3-yl]-thiophene-2-carboxylic acid (tetrahydropyran-2-yloxy)amide | 656224-60-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-[1-(3-phenyl-propyl)-1H-pyrazol-3-yl]-thiophene-2-carboxylic acid (tetrahydropyran-2-yloxy)amide
• 英文别名: N-(oxan-2-yloxy)-5-[1-(3-phenylpropyl)pyrazol-3-yl]thiophene-2-carboxamide
• CAS: 656224-60-1
• 化学式: C₂₂H₂₅N₃O₃S
• 分子量: 411.525
• InChiKey: UTYCDTILCNYZGA-UHFFFAOYSA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  93.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[1-(3-phenyl-propyl)-1H-pyrazol-3-yl]-thiophene-2-carboxylic acid (tetrahydropyran-2-yloxy)amide 在 Amberlyst 15 ion exachange resin 作用下， 以 甲醇 为溶剂， 生成 5-[1-(3-phenyl-propyl)-1H-pyrazol-3-yl]-thiophene-2-carboxylic acid hydroxamide
  参考文献：
  名称：

  [EN] SUBSTITUTED THIENYL-HYDROXAMIC ACIDS AS HISTONE DEACETYLASE INHIBITORS
  [FR] ACIDES SUBSTITUES THIENYLHYDROXAMIQUES UTILISES EN TANT QU'INHIBITEURS D'HISTONE DESACETYLASE

  摘要：

  化合物的化学式（I）：可用于治疗与组蛋白去乙酰化酶活性相关的疾病。

  公开号：

  WO2004013130A1
• 作为产物：
  描述：

  5-(1H-pyrazol-3-yl)-thiophene-2-carbonitrile 在 sodium hydroxide 、 potassium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 5-[1-(3-phenyl-propyl)-1H-pyrazol-3-yl]-thiophene-2-carboxylic acid (tetrahydropyran-2-yloxy)amide
  参考文献：
  名称：

  Identification and optimisation of a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors

  摘要：

  Optimisation of ADS100380, a sub-micromolar HDAC inhibitor identified using a virtual screening approach, led to a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids (6a-i), that possessed significant HDAC inhibitory activity. Subsequent functionalisation of the pendent phenyl group of compounds 6f and 6g provided analogues 6j-w with further enhanced enzyme and anti-proliferative activity. Compound 6j demonstrated efficacy in a mouse xenograft experiment. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.048

文献信息

• [EN] SUBSTITUTED THIENYL-HYDROXAMIC ACIDS AS HISTONE DEACETYLASE INHIBITORS<br/>[FR] ACIDES SUBSTITUES THIENYLHYDROXAMIQUES UTILISES EN TANT QU'INHIBITEURS D'HISTONE DESACETYLASE
  申请人：ARGENTA DISCOVERY LTD

  公开号：WO2004013130A1

  公开（公告）日：2004-02-12

  A compound of formula (I): which can be used in the treatment of diseases associated with histone deacetylase enzymatic activity.

  化合物的化学式（I）：可用于治疗与组蛋白去乙酰化酶活性相关的疾病。
• Identification and optimisation of a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors
  作者：Steve Price、Walter Bordogna、Richard J. Bull、David E. Clark、Peter H. Crackett、Hazel J. Dyke、Matthew Gill、Neil V. Harris、Julia Gorski、Julia Lloyd、Peter M. Lockey、Julia Mullett、Alan G. Roach、Fabien Roussel、Anne B. White

  DOI：10.1016/j.bmcl.2006.10.048

  日期：2007.1

  Optimisation of ADS100380, a sub-micromolar HDAC inhibitor identified using a virtual screening approach, led to a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids (6a-i), that possessed significant HDAC inhibitory activity. Subsequent functionalisation of the pendent phenyl group of compounds 6f and 6g provided analogues 6j-w with further enhanced enzyme and anti-proliferative activity. Compound 6j demonstrated efficacy in a mouse xenograft experiment. (c) 2006 Elsevier Ltd. All rights reserved.