N-cyclopropyl-2-(biphenyl-4-yl)-3-(4-((1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl) phenyl)acrylamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: N-cyclopropyl-2-(biphenyl-4-yl)-3-(4-((1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl) phenyl)acrylamide
• 英文别名: N-cyclopropyl-3-[4-[(E)-3-(hydroxyamino)-3-oxoprop-1-enyl]phenyl]-2-(4-phenylphenyl)prop-2-enamide
• 化学式: C₂₇H₂₄N₂O₃
• 分子量: 424.499
• InChiKey: MRHALQGRBUHYLY-SICOOSAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  78.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-联苯乙酸 在 盐酸羟胺 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 乙酸酐 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 N-cyclopropyl-2-(biphenyl-4-yl)-3-(4-((1E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl) phenyl)acrylamide
  参考文献：
  名称：

  Orally available stilbene derivatives as potent HDAC inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts

  摘要：

  Herein we report the synthesis and activity of a novel class of HDAC inhibitors based on 2, 3-diphenyl acrylic acid derivatives. The compounds in this series have shown to be potent HDAC inhibitors possessing significant antiproliferative activity. Further compounds in this series were subjected to metabolic stability in human liver microsomes (HLM), mouse liver microsomes (MLM), and exhibits promising stability in both. These efforts culminated with the identification of a developmental candidate (5a), which displayed desirable PK/PD relationships, significant efficacy in the xenograft models and attractive ADME profiles. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.014

文献信息

• Orally available stilbene derivatives as potent HDAC inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts
  作者：Virendra Kachhadia、Sridharan Rajagopal、Thanasekaran Ponpandian、Radhakrishnan Vignesh、Karnambaram Anandhan、Daivasigamani Prabhu、Praveen Rajendran、Saranya Nidhyanandan、Anshu Mittal Roy、Fakrudeen Ali Ahamed、Narayanan Surendran、Sriram Rajagopal、Shridhar Narayanan、Balasubramanian Gopalan

  DOI：10.1016/j.ejmech.2015.11.014

  日期：2016.1

  Herein we report the synthesis and activity of a novel class of HDAC inhibitors based on 2, 3-diphenyl acrylic acid derivatives. The compounds in this series have shown to be potent HDAC inhibitors possessing significant antiproliferative activity. Further compounds in this series were subjected to metabolic stability in human liver microsomes (HLM), mouse liver microsomes (MLM), and exhibits promising stability in both. These efforts culminated with the identification of a developmental candidate (5a), which displayed desirable PK/PD relationships, significant efficacy in the xenograft models and attractive ADME profiles. (C) 2015 Elsevier Masson SAS. All rights reserved.