4-((3-formyl-2-methyl-1H-indol-1-yl)methyl)benzoic acid

• 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-formyl-2-methyl-1H-indol-1-yl)methyl)benzoic acid
• 英文别名: 4-[(3-Formyl-2-methylindol-1-yl)methyl]benzoic acid
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: QULRMWKUMOKETM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-((3-formyl-2-methyl-1H-indol-1-yl)methyl)benzoic acid 在 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 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 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 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
• 作为产物：
  描述：

  2-甲基吲哚-3-甲醛 在 sodium hydride 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 4-((3-formyl-2-methyl-1H-indol-1-yl)methyl)benzoic acid
  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

• Design, Synthesis and Cytotoxicity Evaluation of Novel Indole Derivatives Containing Benzoic Acid Group as Potential AKR1C3 Inhibitors
  作者：Mingjiao Sun、Yi Zhou、Xuefang Zhuo、Sheng Wang、Shisheng Jiang、Zhihuan Peng、Ke Kang、Xuehua Zheng、Mingna Sun

  DOI：10.1002/cbdv.202000519

  日期：2020.12

  implicated in drug resistance and has been regarded as a potential therapeutic target. Here we examined a series of indole derivatives containing benzoic acid or phenylhydroxamic acid and found that 4‐(3‐[(3,4,5‐trimethoxyphenyl)sulfanyl]‐1H‐indol‐1‐yl}methyl)benzoic acid (3e) and N‐hydroxy‐4‐(3‐[(3,4,5‐trimethoxyphenyl)sulfanyl]‐1H‐indol‐1‐yl}methyl)benzamide (3q) inhibited 22Rv1 cell proliferation with IC50

  去势抵抗性前列腺癌 (CRPC) 是一种致命的转移性前列腺癌，其特征是雄激素轴的重新激活。醛酮还原酶 1C3 (AKR1C3) 分别将雄烯二酮 (AD) 和 5α-雄甾烷二酮转化为睾酮 (T) 和 5α-二氢睾酮 (DHT)。在 CRPC 中，AKR1C3 上调并与耐药性有关，已被视为潜在的治疗靶点。在这里，我们检查了一系列含有苯甲酸或苯异羟肟酸的吲哚衍生物，发现 4-(3-[(3,4,5-三甲氧基苯基)硫烷基]-1H-吲哚-1-基}甲基)苯甲酸 (3e ) 和 N-羟基-4-(3-[(3,4,5-三甲氧基苯基)硫烷基]-1H-吲哚-1-基}甲基)苯甲酰胺 (3q) 抑制 22Rv1 细胞增殖，IC50 值为 6.37 μM 和分别为 2.72 μM。在酶促测定中，化合物 3e 和 3q 对 AKR1C3 表现出有效的抑制作用（IC50 分别为 0.26 和 2.39 μM）。这些结果表明，化合物
• Ring-opened tetrahydro-γ-carbolines display cytotoxicity and selectivity with histone deacetylase isoforms
  作者：Kunal Nepali、Hsueh-Yun Lee、Mei-Jung Lai、Ritu Ojha、Tung-Yun Wu、Gu-Xian Wu、Mei-Chuan Chen、Jing-Ping Liou

  DOI：10.1016/j.ejmech.2016.12.039

  日期：2017.2

  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.