5-phenyl-thiophene-2-carboxylic acid (tetrahydro-pyran-2-yloxy)-amide

• 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-phenyl-thiophene-2-carboxylic acid (tetrahydro-pyran-2-yloxy)-amide
• 英文别名: N-(oxan-2-yloxy)-5-phenylthiophene-2-carboxamide
• 化学式: C₁₆H₁₇NO₃S
• 分子量: 303.382
• InChiKey: ZPZQHSSBULQTBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  75.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-phenyl-thiophene-2-carboxylic acid (tetrahydro-pyran-2-yloxy)-amide 生成 5-phenyl-thiophene-2-carboxylic acid hydroxamide
  参考文献：
  名称：

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

  摘要：

  Further investigation of a series of thienyl-based hydroxamic acids that included ADS 100380 and ADS 102550 led to the identification of the 5-pyridin-2-yl-thiophene-2-hydroxamic acid 3c, which possessed modest HDAC inhibitory activity. Substitution at the 5- and 6-positions of the pyridyl ring of compound 3c provided compounds 5a-g, 7a, b, 9, and 13a. Compound 5b demonstrated improved potency, in vitro DMPK profile, and rat oral bioavailability, compared to ADS 102550. Functionalisation of the pendent phenyl group of compounds 5b, 5e and 13a provided analogues that possessed excellent enzyme inhibition and anti-proliferative activity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.045
• 作为产物：
  描述：

  O-(四氢-2H-吡喃-2-基)羟基胺 、 5-苯基噻吩-2-羧酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 7.0h， 以81%的产率得到5-phenyl-thiophene-2-carboxylic acid (tetrahydro-pyran-2-yloxy)-amide
  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

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-pyridin-2-yl-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors
  作者：Steve Price、Walter Bordogna、Ruth Braganza、Richard J. Bull、Hazel J. Dyke、Sophie Gardan、Matthew Gill、Neil V. Harris、Robert A. Heald、Marco van den Heuvel、Peter M. Lockey、Julia Lloyd、Aranzazu G. Molina、Alan G. Roach、Fabien Roussel、Jonathan M. Sutton、Anne B. White

  DOI：10.1016/j.bmcl.2006.10.045

  日期：2007.1

  Further investigation of a series of thienyl-based hydroxamic acids that included ADS 100380 and ADS 102550 led to the identification of the 5-pyridin-2-yl-thiophene-2-hydroxamic acid 3c, which possessed modest HDAC inhibitory activity. Substitution at the 5- and 6-positions of the pyridyl ring of compound 3c provided compounds 5a-g, 7a, b, 9, and 13a. Compound 5b demonstrated improved potency, in vitro DMPK profile, and rat oral bioavailability, compared to ADS 102550. Functionalisation of the pendent phenyl group of compounds 5b, 5e and 13a provided analogues that possessed excellent enzyme inhibition and anti-proliferative activity. (c) 2006 Elsevier Ltd. All rights reserved.