5-hydroxy-N-phenylpentanamide | 606092-23-3

• 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: 5-hydroxy-N-phenylpentanamide
• 英文别名: 6-hydroxy-N-phenyl-hexanamide；6-hydroxy-N-phenylhexanamide
• CAS: 606092-23-3
• 化学式: C₁₂H₁₇NO₂
• 分子量: 207.272
• InChiKey: HZDDGRKUJWBIOO-UHFFFAOYSA-N

物化性质

• 沸点：
  417.6±28.0 °C(Predicted)
• 密度：
  1.114±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 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：

  5-hydroxy-N-phenylpentanamide 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 以91%的产率得到6-溴-N-苯基己酰胺
  参考文献：
  名称：

  内酯有机催化开环氨解法无金属合成N-芳基酰胺

  摘要：

  生物来源的非应变内酯与芳族胺的催化开环可以提供一种直接的，100％原子经济且可持续的通往相关N芳基酰胺支架的途径。在此，据报道，在温和的操作条件下，使用有机双环胍催化剂，由反应性较差的芳族胺和非应变的内酯首次形成了无金属且高效的N-芳基酰胺。该协议具有很高的应用潜力，例如与药物相关的分子的形式合成。

  DOI：

  10.1002/cssc.201700415
• 作为产物：
  描述：

  甲基脂肪酰氯 在 lithium aluminium tetrahydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 5-hydroxy-N-phenylpentanamide
  参考文献：
  名称：

  Phosphorus-Based SAHA Analogues as Histone Deacetylase Inhibitors

  摘要：

  graphicThree analogues of suberoyl anilide hydroxamic acid (SAHA) with phosphorus metal-chelating functionalities were synthesized as inhibitors of histone deacetylases (HDACs). The compounds showed weak activity for HeLa nuclear extracts (IC50 = 0.57-6.1 mM), HDAC8 (IC50 = 0.28-0.41 mM), and histone-deacetylase-like protein (HDLP, IC50 = 0.33-1.9 mM), suggesting that the transition state of HDAC is not analogous to zinc proteases. Anti proliferative activity against A2780 cancer cells (IC50 = 0.11-0.12 mM), comparable to SAHA (0.15 mM), was observed.

  DOI：

  10.1021/ol035056n

文献信息

• Inhibitors of histone deacetylase
  申请人：——

  公开号：US20020177594A1

  公开（公告）日：2002-11-28

  Compounds having the formula 1 or therapeutically acceptable salts thereof, are histone deacetylase (HDAC) inhibitors. Preparation of the compounds, compositions containing the compounds, and treatment of diseases using the compounds are disclosed.

  具有以下化学式的化合物或其治疗上可接受的盐是组蛋白去乙酰化酶（HDAC）抑制剂。本文揭示了该化合物的制备、含有该化合物的组合物以及使用该化合物治疗疾病的方法。
• Organotin-catalyzed synthesis of hydroxyalkylamides from lactones via a ring-opening process
  作者：Xiayu Liang、Peng Yu、Chen Fu、Yongcun Shen

  DOI：10.1016/j.tetlet.2021.152821

  日期：2021.3

  A new strategy for the facile synthesis of hydroxyalkylamides through the ring-opening reaction of lactone with amine promoted by dibutyltin acetate was developed. A series of hydroxyalkylamide compounds were obtained and the method was successfully applied to the synthesis of pharmaceutically active molecules tyrosinase inhibitor V and HDAC inhibitor VI via a three-step synthetic pathway. The broad

  提出了通过乙酸二丁锡促进内酯与胺的开环反应轻松合成羟烷基酰胺的新策略。获得了一系列羟烷基酰胺化合物，并将该方法成功地通过三步合成途径用于合成药物活性分子酪氨酸酶抑制剂V和HDAC抑制剂VI。广泛的底物范围，温和的反应条件和实际应用证明了该方法的有效性，兼容性和实用性。
• Structural Requirements of HDAC Inhibitors: SAHA Analogues Modified at the C2 Position Display HDAC6/8 Selectivity
  作者：Ahmed T. Negmeldin、Geetha Padige、Anton V. Bieliauskas、Mary Kay H. Pflum

  DOI：10.1021/acsmedchemlett.6b00124

  日期：2017.3.9

  Histone deacetylase (HDAC) proteins are epigenetic regulators that deacetylate protein substrates, leading to subsequent changes in cell function. HDAC proteins are implicated in cancers, and several HDAC inhibitors have been approved by the FDA as anticancer drugs, including SAHA (suberoylanilide hydroxamic acid; Vorinostat and Zolinza). Unfortunately, SAHA inhibits most HDAC isoforms, which limits

  组蛋白脱乙酰基酶（HDAC）蛋白是使蛋白质底物脱乙酰基的表观遗传调节剂，从而导致细胞功能发生随后的变化。HDAC蛋白与癌症有关，FDA已批准了几种HDAC抑制剂作为抗癌药物，包括SAHA（亚磺酰苯胺异羟肟酸；伏立诺他和Zolinza）。不幸的是，SAHA抑制了大多数HDAC亚型，这限制了其用作药理学工具的使用，并可能导致临床副作用。在这项工作中，合成了在C2位置取代的SAHA类似物，并在体外和细胞中筛选了HDAC同工型的选择性。与HDAC1，-2和-3相比，最有力和选择性的化合物C2-正己基SAHA对HDAC6和HDAC8表现出亚微摩尔效价，对HDAC6和HDAC8的选择性为49到300倍。对接研究为选择性提供了结构上的理由。
• Synthesis and biological evaluation of aziridin-1-yl oxime-based vorinostat analogs as anticancer agents
  作者：Anna Nikitjuka、Irina Shestakova、Nadezhda Romanchikova、Aigars Jirgensons

  DOI：10.1007/s10593-015-1752-z

  日期：2015.7

  The suberoyl anilide hydroxamic acid (vorinostat) analogs with the aziridin-1-yl oxime moiety as a possible metal chelating functionality have been synthesized. Their biological activity and stability under physiological conditions have been evaluated. Although some of the synthesized compounds demonstrated high antiproliferative activity against human HT1080 fibrosarcoma (HT1080, IC50 0.3-7.7 mu M) comparable to vorinostat (HT1080, IC50 2.4 mu M), they showed only weak histone deacetylase inhibition activity in HeLa cell line extracts.
• Structural requirements of HDAC inhibitors: SAHA analogs functionalized adjacent to the hydroxamic acid
  作者：Anton V. Bieliauskas、Sujith V.W. Weerasinghe、Mary Kay H. Pflum

  DOI：10.1016/j.bmcl.2007.01.117

  日期：2007.4

  Inhibitors of histone deacetylase (HDAC) proteins such as suberoylanilide hydroxamic acid (SAHA) have emerged as effective therapeutic anti-cancer agents. To better understand the structural requirements of HDAC inhibitors, a small molecule library with a variety of substituents attached adjacent to the metal binding hydroxamic acid of SAHA was synthesized. The presence of a substituent adjacent to the hydroxamic acid led to an 800- to 5000-fold decrease in inhibition compared to SAHA. The observed results have implications for drug design, suggesting that HDAC inhibitors with substituents near the metal binding moiety will have inhibitory activities in the micromolar rather than nanomolar range. (c) 2007 Elsevier Ltd. All rights reserved.