(E)-N-hydroxy-4-butoxy-2-phenylcinnamamide | 1417998-19-6

• 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: (E)-N-hydroxy-4-butoxy-2-phenylcinnamamide
• 英文别名: (E)-3-(4-butoxy-2-phenylphenyl)-N-hydroxyprop-2-enamide
• CAS: 1417998-19-6
• 化学式: C₁₉H₂₁NO₃
• 分子量: 311.381
• InChiKey: GDWUUICQMQDJMP-ZRDIBKRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  7-Butoxycoumarin 在 吡啶 、 四(三苯基膦)钯 、 羟胺 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (E)-N-hydroxy-4-butoxy-2-phenylcinnamamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation ofortho-ArylN-Hydroxycinnamides as Potent Histone Deacetylase (HDAC) 8 Isoform-Selective Inhibitors

  摘要：

  AbstractHistone deacetylases (HDACs) are a family of enzymes that play a crucial role in biological process and diseases. In contrast to other isozymes, HDAC8 is uniquely incapable of histone acetylation. In order to delineate its physiological function, we developed HDAC8‐selective inhibitors using knowledge‐based design combined with structural modeling techniques. Enzyme inhibitory analysis demonstrated that some of the resulting compounds (22 b, 22 d, 22 f, and 22 g) exhibited anti‐HDAC8 activity superior to PCI34051, a known HDAC8‐specific inhibitor, with IC50 values in the range of 5–50 nM. Among them, compound 22 d showed antiproliferative effects toward several human lung cancer cell lines (A549, H1299, and CL1‐5); it exhibited cytotoxicity against human lung CL1‐5 cells similar to that of SAHA yet without significant cytotoxicity for normal IMR‐90 cells. Expression profiling of HDAC isoforms in three cancer cell lines indicated that the HDAC8 level in CL1‐5 is higher than that in H1299 and CL1‐1 cells, a result consistent with the differential cytotoxicity of compound 22 d. These results suggest the effectiveness of our design concept, which may lead to a tool compound for studying the specific role of HDAC8 in cellular biological processes.

  DOI：

  10.1002/cmdc.201200300

文献信息

• [EN] DERIVATIVES OF 1 H-PYRAZOLO[3,4-B]PYRIDINE AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF PROLIFERATIVE DISORDERS<br/>[FR] DÉRIVÉS DE 1H-PYRAZOLO[3,4-B]PYRIDINE ET SES COMPOSITIONS PHARMACEUTIQUES PERMETTANT LE TRAITEMENT DE TROUBLES PROLIFÉRATIFS
  申请人：GALAPAGOS NV

  公开号：WO2015024905A1

  公开（公告）日：2015-02-26

  The present invention discloses compounds according to Formula (I): wherein R1, R2, R3, R4, L, and X are as defined herein. The present invention relates to compounds,methods for their production, pharmaceutical compositions comprising the same, and their use in the prophylaxis and/or treatment of inflammatory conditions, type 2 diabetes, neurological and/or neurodegenerative diseases, autoimmune diseases, proliferative diseases (in particular metastatic diseases, and/or cancer), abnormal angiogenesis associated diseases, degradation of cartilage, and/or disruption of cartilage homeostasis, in particular in the prophylaxis and/or treatment of cancer. The present invention also discloses methods of treatment using the same compounds, for the prophylaxis and/or treatment of said diseases by administering the compound of the invention.

  本发明公开了根据以下式（I）的化合物：其中R1、R2、R3、R4、L和X如本文所定义。本发明涉及化合物、其生产方法、包含相同化合物的药物组合物，以及它们在预防和/或治疗炎症性疾病、2型糖尿病、神经和/或神经退行性疾病、自身免疫疾病、增生性疾病（特别是转移性疾病和/或癌症）、异常血管生成相关疾病、软骨降解和/或软骨稳态紊乱，特别是在预防和/或治疗癌症方面的用途。本发明还公开了使用相同化合物的治疗方法，通过给予本发明化合物的方式预防和/或治疗上述疾病。
• HDAC8 inhibitors for treating cancer
  申请人：City of Hope

  公开号：US10308596B2

  公开（公告）日：2019-06-04

  Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8.

  本文特别提供了通过抑制 HDAC8 治疗癌症的化合物和方法。
• DERIVATIVES OF 1 H-PYRAZOLO[3,4-B]PYRIDINE AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
  申请人：Galapagos NV

  公开号：EP3036234A1

  公开（公告）日：2016-06-29
• HDAC8 INHIBITORS FOR TREATING CANCER
  申请人：City of Hope

  公开号：US20190322617A1

  公开（公告）日：2019-10-24

  Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8.
• Synthesis and Biological Evaluation of<i>ortho</i>-Aryl<i>N</i>-Hydroxycinnamides as Potent Histone Deacetylase (HDAC) 8 Isoform-Selective Inhibitors
  作者：Wei-Jan Huang、Yi-Ching Wang、Shi-Wei Chao、Chen-Yui Yang、Liang-Chieh Chen、Mei-Hsiang Lin、Wen-Chi Hou、Mei-Yu Chen、Tai-Lin Lee、Ping Yang、Chung-I Chang

  DOI：10.1002/cmdc.201200300

  日期：2012.10

  AbstractHistone deacetylases (HDACs) are a family of enzymes that play a crucial role in biological process and diseases. In contrast to other isozymes, HDAC8 is uniquely incapable of histone acetylation. In order to delineate its physiological function, we developed HDAC8‐selective inhibitors using knowledge‐based design combined with structural modeling techniques. Enzyme inhibitory analysis demonstrated that some of the resulting compounds (22 b, 22 d, 22 f, and 22 g) exhibited anti‐HDAC8 activity superior to PCI34051, a known HDAC8‐specific inhibitor, with IC50 values in the range of 5–50 nM. Among them, compound 22 d showed antiproliferative effects toward several human lung cancer cell lines (A549, H1299, and CL1‐5); it exhibited cytotoxicity against human lung CL1‐5 cells similar to that of SAHA yet without significant cytotoxicity for normal IMR‐90 cells. Expression profiling of HDAC isoforms in three cancer cell lines indicated that the HDAC8 level in CL1‐5 is higher than that in H1299 and CL1‐1 cells, a result consistent with the differential cytotoxicity of compound 22 d. These results suggest the effectiveness of our design concept, which may lead to a tool compound for studying the specific role of HDAC8 in cellular biological processes.