(E)-3-(3-(1H-indol-1-ylsulfonyl)phenyl)-N-hydroxyacrylamide | 1609171-90-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(3-(1H-indol-1-ylsulfonyl)phenyl)-N-hydroxyacrylamide
• 英文别名: (E)-N-hydroxy-3-(3-indol-1-ylsulfonylphenyl)prop-2-enamide
• CAS: 1609171-90-5
• 化学式: C₁₇H₁₄N₂O₄S
• 分子量: 342.375
• InChiKey: IKMBILRCONHQHD-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  96.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-(1H-indol-1-ylsulfonyl)benzaldehyde 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (E)-3-(3-(1H-indol-1-ylsulfonyl)phenyl)-N-hydroxyacrylamide
  参考文献：
  名称：

  Azaindolylsulfonamides, with a More Selective Inhibitory Effect on Histone Deacetylase 6 Activity, Exhibit Antitumor Activity in Colorectal Cancer HCT116 Cells

  摘要：

  A series of indolylsulfonylcinnamic hydroxamates has been synthesized. Compound 12, (E)-3-(3-((1H-pyrrolo[2,3-b]pyridin-1-yl)sulfonyl)phenyl)-N-hydroxyacrylamide, which has a 7-azaindole core cap, was shown to have antiproliferative activity against KB, H460, PC3, HSC-3, HONE-1, A549, MCF-7, TSGH, MKN45, HT29, and HCT116 human cancer cell lines. Pharmacological studies indicated that 12 functions as a potent HDAC inhibitor with an IC50 value of 0.1 mu M. It is highly selective for histone deacetylase 6 (HDAC6) and is 60-fold more active than against HDAC1 and 223-fold more active than against HDAC2. It has a good pharmacokinetic profile with oral bioavailability of 33%. In in vivo efficacy evaluations in colorectal HCT116 xenografts, compound 12 suppresses tumor growth more effectively than SAHA (1, N-hydroxy-N'-phenyloctanediamide) and is therefore seen as a suitable candidate for further investigation.

  DOI：

  10.1021/jm401899x

文献信息

• Histone deacetylase inhibitors
  申请人：Taipei Medical University

  公开号：US10246455B2

  公开（公告）日：2019-04-02

  Fused bicycle indol, indoline, azoindole, or azoindoline compounds of Formula (I) set forth herein. Also disclosed are pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing the same. Further disclosed is a method for treating cancer, e.g., glioma, prostate cancer, and colorectal cancer, with these compounds.

  式（I）的融合自行车吲哚、吲哚啉、偶氮吲哚或偶氮吲哚啉化合物。还公开了这些化合物的药学上可接受的盐和含有这些化合物的药物组合物。进一步公开了一种用这些化合物治疗癌症，如胶质瘤、前列腺癌和结直肠癌的方法。
• Synthesis of small molecule histone deacetylase 6 degraders, compounds formed thereby, and pharmaceutical compositions containing them
  申请人：Wisconsin Alumni Research Foundation

  公开号：US11059815B2

  公开（公告）日：2021-07-13

  Histone deacetylase (“HDAC”)-selective inhibitors covalently bonded to a linker covalently bonded to an E3 ubiquitin ligase ligand, and salts thereof; pharmaceutical compositions containing them; methods of using the composition to inhibit neoplastic cell growth in mammals, including humans.

  组蛋白去乙酰化酶（"HDAC"）选择性抑制剂，共价键合到与 E3 泛素配体共价键合的连接体上，及其盐类；含有它们的药物组合物；使用该组合物抑制哺乳动物（包括人类）肿瘤细胞生长的方法。
• HISTONE DEACETYLASE INHIBITORS
  申请人：Yen Yun

  公开号：US20170057956A1

  公开（公告）日：2017-03-02

  Fused bicycle indol, indoline, azoindole, or azoindoline compounds of Formula (I) set forth herein. Also disclosed are pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing the same. Further disclosed is a method for treating cancer, e.g., glioma, prostate cancer, and colorectal cancer, with these compounds.
• SYNTHESIS OF SMALL MOLECULE HISTONE DEACETYLASE 6 DEGRADERS, COMPOUNDS FORMED THEREBY, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：Wisconsin Alumni Research Foundation

  公开号：US20200190079A1

  公开（公告）日：2020-06-18

  Histone deacetylase (“HDAC”)-selective inhibitors covalently bonded to a linker covalently bonded to an E3 ubiquitin ligase ligand, and salts thereof; pharmaceutical compositions containing them; methods of using the composition to inhibit neoplastic cell growth in mammals, including humans.
• Azaindolylsulfonamides, with a More Selective Inhibitory Effect on Histone Deacetylase 6 Activity, Exhibit Antitumor Activity in Colorectal Cancer HCT116 Cells
  作者：Hsueh-Yun Lee、An-Chi Tsai、Mei-Chuan Chen、Po-Jung Shen、Yun-Ching Cheng、Ching-Chuan Kuo、Shiow-Lin Pan、Yi-Min Liu、Jin-Fen Liu、Teng-Kuang Yeh、Jing-Chi Wang、Chi-Yen Chang、Jang-Yang Chang、Jing-Ping Liou

  DOI：10.1021/jm401899x

  日期：2014.5.22

  A series of indolylsulfonylcinnamic hydroxamates has been synthesized. Compound 12, (E)-3-(3-((1H-pyrrolo[2,3-b]pyridin-1-yl)sulfonyl)phenyl)-N-hydroxyacrylamide, which has a 7-azaindole core cap, was shown to have antiproliferative activity against KB, H460, PC3, HSC-3, HONE-1, A549, MCF-7, TSGH, MKN45, HT29, and HCT116 human cancer cell lines. Pharmacological studies indicated that 12 functions as a potent HDAC inhibitor with an IC50 value of 0.1 mu M. It is highly selective for histone deacetylase 6 (HDAC6) and is 60-fold more active than against HDAC1 and 223-fold more active than against HDAC2. It has a good pharmacokinetic profile with oral bioavailability of 33%. In in vivo efficacy evaluations in colorectal HCT116 xenografts, compound 12 suppresses tumor growth more effectively than SAHA (1, N-hydroxy-N'-phenyloctanediamide) and is therefore seen as a suitable candidate for further investigation.