7-[(1,4,4-trimethyl-3,4-dihydrocarbostyril-6-carbonyl)amino]heptanoic acid hydroxyamide | 1616590-11-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-[(1,4,4-trimethyl-3,4-dihydrocarbostyril-6-carbonyl)amino]heptanoic acid hydroxyamide
• 英文别名: N-[7-(hydroxyamino)-7-oxoheptyl]-1,4,4-trimethyl-2-oxo-3H-quinoline-6-carboxamide
• CAS: 1616590-11-4
• 化学式: C₂₀H₂₉N₃O₄
• 分子量: 375.468
• InChiKey: KSXJIIICYHHPTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  98.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 羟胺 、 sodium methylate 作用下， 以 甲醇 、 水 为溶剂， 反应 1.07h， 生成 7-[(1,4,4-trimethyl-3,4-dihydrocarbostyril-6-carbonyl)amino]heptanoic acid hydroxyamide
  参考文献：
  名称：

  Design and synthesis of novel and highly-active pan-histone deacetylase (pan-HDAC) inhibitors

  摘要：

  Histone deacetylase (HDAC) inhibitions are known to elicit anticancer effects. We designed and synthesized several HDAC inhibitors. Among these compounds, compound 40 exhibited a more than 10-fold stronger inhibitory activity compared with that of suberoylanilide hydroxamic acid (SAHA) against each human HDAC isozyme in vitro (IC50 values of 40: HDAC1, 0.0038μM; HDAC2, 0.0082μM; HDAC3, 0.015μM; HDAC8, 0.0060μM; HDAC4, 0.058μM; HDAC9, 0.0052μM; HDAC6, 0.058μM). The dose of the administered HDAC inhibitors that contain hydroxamic acid as the zinc-binding group may be reduced by 40. Because the carbostyril subunit is a time-tested structural component of drugs and biologically active compounds, 40 most likely exhibits good absorption, distribution, metabolism, excretion, and toxicity (ADMET). Thus, compound 40 is expected to be a promising therapeutic agent or chemical tool for the investigation of life process.

  DOI：

  10.1016/j.bmc.2014.05.001

文献信息

• [EN] HYDROXAMIC ACID DERIVATIVE OR SALT THEREOF<br/>[FR] DÉRIVÉ DE L'ACIDE HYDROXAMIQUE OU SEL ASSOCIÉ
  申请人：NIPPON PHARMACEUTICAL CHEMICALS CO LTD

  公开号：WO2014196328A1

  公开（公告）日：2014-12-11

  　本発明は、ヒストン脱アセチル化酵素阻害剤として有用なヒドロキサム酸誘導体またはその塩を提供することを主な目的とする。さらに、本発明は、ヒドロキサム酸誘導体またはその塩を有効成分として含む医薬組成物、ヒストン脱アセチル化酵素阻害剤、及び抗腫瘍剤を提供することも目的とする。　本発明のヒドロキサム酸誘導体またはその塩は、下記一般式（Ａ）で表される。
• Design and synthesis of novel and highly-active pan-histone deacetylase (pan-HDAC) inhibitors
  作者：Toshihiko Tashima、Hiroaki Murata、Hidehiko Kodama

  DOI：10.1016/j.bmc.2014.05.001

  日期：2014.7

  Histone deacetylase (HDAC) inhibitions are known to elicit anticancer effects. We designed and synthesized several HDAC inhibitors. Among these compounds, compound 40 exhibited a more than 10-fold stronger inhibitory activity compared with that of suberoylanilide hydroxamic acid (SAHA) against each human HDAC isozyme in vitro (IC50 values of 40: HDAC1, 0.0038μM; HDAC2, 0.0082μM; HDAC3, 0.015μM; HDAC8, 0.0060μM; HDAC4, 0.058μM; HDAC9, 0.0052μM; HDAC6, 0.058μM). The dose of the administered HDAC inhibitors that contain hydroxamic acid as the zinc-binding group may be reduced by 40. Because the carbostyril subunit is a time-tested structural component of drugs and biologically active compounds, 40 most likely exhibits good absorption, distribution, metabolism, excretion, and toxicity (ADMET). Thus, compound 40 is expected to be a promising therapeutic agent or chemical tool for the investigation of life process.