4-((3-((dimethylamino)methyl)-2-methyl-1H-indol-1-yl)methyl)-N-hydroxybenzamide | 1392835-46-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-((3-((dimethylamino)methyl)-2-methyl-1H-indol-1-yl)methyl)-N-hydroxybenzamide
• 英文别名: 4-[[3-[(dimethylamino)methyl]-2-methylindol-1-yl]methyl]-N-hydroxybenzamide
• CAS: 1392835-46-9
• 化学式: C₂₀H₂₃N₃O₂
• 分子量: 337.422
• InChiKey: AWFYSKUENHXUOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-甲基吲哚-3-甲醛 在 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 4-((3-((dimethylamino)methyl)-2-methyl-1H-indol-1-yl)methyl)-N-hydroxybenzamide
  参考文献：
  名称：

  Ring-opened tetrahydro-γ-carbolines display cytotoxicity and selectivity with histone deacetylase isoforms

  摘要：

  This study is focused on modification of the indole moiety and the N1-zinc binding domain of tubastatin A, and the effects of such changes on biological activity. Fourteen N-substituted indoles (5-18) were synthesized and structure -activity relationship studies indicated that the change of the tetrahydro-gamma-carboline in tubastatin A led to substituted indoles (compounds 7, 11, and 15) which showed significant improvements of selective inhibition for HDAC6 over HDAC1 and HDAC2 in comparison to ACY1215, a compound undergoing clinical trials. In addition, attachment of different hydroxamic acid groups, the zinc binding motif at the N1 position, contributes to the antiproliferative activity in cancer cells. Several synthetic compounds exhibited potent growth inhibition in a broad spectrum of tumor cell lines, induced irreversible growth arrest capacities by suppressing colony formation ability and activated the apoptosis pathway. The data provide compelling evidence that our newly synthesized compounds with type B to D hydroxamic acid groups as the zinc binding motif at the N1 position are potent selective inhibitors of HDAC6 and could be investigated preclinically as potential anticancer drugs. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.12.039

文献信息

• HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
  申请人：Kozikowski Alan

  公开号：US20140128408A1

  公开（公告）日：2014-05-08

  Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a peripheral neuropathy, a neurological disease, traumatic brain injury, stroke, hypertension, malaria, an autoimmune disease, autism, autism spectrum disorders, and inflammation, also are disclosed.

  本发明公开了组蛋白去乙酰化酶抑制剂（HDACIs）及其组成物。公开了治疗疾病和状况的方法，其中抑制HDAC提供了益处，如癌症、神经退行性疾病、周围神经病变、神经疾病、创伤性脑损伤、中风、高血压、疟疾、自身免疫疾病、自闭症、自闭症谱系障碍和炎症。
• N-HYDROXYBENZAMIDE DERIVATIVES AS HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
  申请人：The Board of Trustees of the University of Illinois

  公开号：EP2670733B1

  公开（公告）日：2019-04-10
• US9249087B2
  申请人：——

  公开号：US9249087B2

  公开（公告）日：2016-02-02
• USRE47009E1
  申请人：——

  公开号：USRE47009E1

  公开（公告）日：2018-08-28
• [EN] HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME<br/>[FR] INHIBITEURS DE HDAC ET PROCÉDÉS THÉRAPEUTIQUES LES UTILISANT
  申请人：UNIV ILLINOIS

  公开号：WO2012106343A2

  公开（公告）日：2012-08-09

  Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a peripheral neuropathy, a neurological disease, traumatic brain injury, stroke, hypertension, malaria, an autoimmune disease, autism, autism spectrum disorders, and inflammation, also are disclosed.