(E)-N-hydroxy-3-(3-(6-methoxy-3-(3,4,5-trimethoxybenzoyl)-1H-indol-1-ylsulfonyl)phenyl)acrylamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (E)-N-hydroxy-3-(3-(6-methoxy-3-(3,4,5-trimethoxybenzoyl)-1H-indol-1-ylsulfonyl)phenyl)acrylamide
• 英文别名: HDAC6/Tubulin Inhibitor MPT0B451；(E)-N-hydroxy-3-[3-[6-methoxy-3-(3,4,5-trimethoxybenzoyl)indol-1-yl]sulfonylphenyl]prop-2-enamide
• 化学式: C₂₈H₂₆N₂O₉S
• 分子量: 566.588
• InChiKey: VYTJGUNWINJKES-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  151
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-溴苯磺酰氯 在 N-甲基吗啉 、 palladium diacetate 、 sodium hydride 、 potassium carbonate 、 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 、 三苯基膦 、 三氟乙酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 (E)-N-hydroxy-3-(3-(6-methoxy-3-(3,4,5-trimethoxybenzoyl)-1H-indol-1-ylsulfonyl)phenyl)acrylamide
  参考文献：
  名称：

  3-Aroylindoles display antitumor activity in vitro and in vivo: Effects of N1-substituents on biological activity

  摘要：

  A series of 3-aroylindole hydroxamic acids (10-17) were developed based on the concept of a structural combination of tubulin and histone deacetylase (HDAC) inhibitors. This was accomplished by introducing hydroxamic acid-containing moieties at the N1 position of the tubulin assembly inhibitor, compound 9 (SCB01A, BPROL075, phase II trial). Most of synthetic compounds produced in this way displayed comparable HDAC inhibitory activity, and four (10, 12-14) of them also inhibit tubulin assembly. Notably, compound 12 possesses not only tubulin and HDAC inhibitory activity but also shows HDAC6 selectivity over other HDAC isoforms. In addition, it exhibits remarkable inhibitory activity against the growth cancer cells in vitro and in vivo (PC3 and RPMI-8226 cells). Notably, it suppresses the growth of multiple myeloma xenografts without leading to the death of teated animals like reference compound. In sum, this study provided potential compounds with safer profiles for cancer treatment. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.11.033

文献信息

• 3-Aroylindoles display antitumor activity in vitro and in vivo: Effects of N1-substituents on biological activity
  作者：Hsueh-Yun Lee、Jiann-Fong Lee、Sunil Kumar、Yi-Wen Wu、Wei-Chun HuangFu、Mei-Jung Lai、Yu-Hsuan Li、Hsiang-Ling Huang、Fei-Chiao Kuo、Che-Jen Hsiao、Chun-Chun Cheng、Chia-Ron Yang、Jing-Ping Liou

  DOI：10.1016/j.ejmech.2016.11.033

  日期：2017.1

  A series of 3-aroylindole hydroxamic acids (10-17) were developed based on the concept of a structural combination of tubulin and histone deacetylase (HDAC) inhibitors. This was accomplished by introducing hydroxamic acid-containing moieties at the N1 position of the tubulin assembly inhibitor, compound 9 (SCB01A, BPROL075, phase II trial). Most of synthetic compounds produced in this way displayed comparable HDAC inhibitory activity, and four (10, 12-14) of them also inhibit tubulin assembly. Notably, compound 12 possesses not only tubulin and HDAC inhibitory activity but also shows HDAC6 selectivity over other HDAC isoforms. In addition, it exhibits remarkable inhibitory activity against the growth cancer cells in vitro and in vivo (PC3 and RPMI-8226 cells). Notably, it suppresses the growth of multiple myeloma xenografts without leading to the death of teated animals like reference compound. In sum, this study provided potential compounds with safer profiles for cancer treatment. (C) 2016 Elsevier Masson SAS. All rights reserved.