N-(6-羟基己基)-1H-吲哚-2-甲酰胺 | 672333-06-1

• 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
• 中文名称: N-(6-羟基己基)-1H-吲哚-2-甲酰胺
• 英文名称: N2-(6-hexanol)-1H-2-indolecarboxamide
• 英文别名: 1H-Indole-2-carboxamide, N-(6-hydroxyhexyl)-；N-(6-hydroxyhexyl)-1H-indole-2-carboxamide
• CAS: 672333-06-1
• 化学式: C₁₅H₂₀N₂O₂
• 分子量: 260.336
• InChiKey: GVXWRMNUFGFSQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  65.1
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(6-羟基己基)-1H-吲哚-2-甲酰胺 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 四溴化碳 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 S-[6-(1H-indole-2-carbonylamino)hexyl] 2-methylpropanethioate
  参考文献：
  名称：

  人组蛋白脱乙酰基酶的新型抑制剂：基于SAHA的非异羟肟酸酯的设计，合成，酶抑制和癌细胞生长抑制。

  摘要：

  为了找到新型的非异羟肟酸酯组蛋白脱乙酰基酶（HDAC）抑制剂，设计并合成了以亚磺酰苯胺异羟肟酸（SAHA）为模型的一系列化合物。在该系列中，发现化合物7（其中SAHA的异羟肟酸被硫醇替代）与SAHA一样有效，该系列的优化导致鉴定出比SAHA更有效的HDAC抑制剂。在癌细胞生长抑制测定中，S-异丁酰基衍生物51显示出强活性，并且其效力与SAHA相当。通过Western印迹分析证实癌细胞生长抑制活性是组蛋白过度乙酰化和随后诱导p21（WAF1 / CIP1）的结果。

  DOI：

  10.1021/jm049207j
• 作为产物：
  描述：

  吲哚-2-羧酸 、 6-氨基-1-己醇 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(6-羟基己基)-1H-吲哚-2-甲酰胺
  参考文献：
  名称：

  人组蛋白脱乙酰基酶的新型抑制剂：基于SAHA的非异羟肟酸酯的设计，合成，酶抑制和癌细胞生长抑制。

  摘要：

  为了找到新型的非异羟肟酸酯组蛋白脱乙酰基酶（HDAC）抑制剂，设计并合成了以亚磺酰苯胺异羟肟酸（SAHA）为模型的一系列化合物。在该系列中，发现化合物7（其中SAHA的异羟肟酸被硫醇替代）与SAHA一样有效，该系列的优化导致鉴定出比SAHA更有效的HDAC抑制剂。在癌细胞生长抑制测定中，S-异丁酰基衍生物51显示出强活性，并且其效力与SAHA相当。通过Western印迹分析证实癌细胞生长抑制活性是组蛋白过度乙酰化和随后诱导p21（WAF1 / CIP1）的结果。

  DOI：

  10.1021/jm049207j

文献信息

• Novel pyrrolo[2,1-c][1,4] benzodiazepine-indole derivatives, their preparation process, and uses of the same
  申请人：Kaohsiung Medical University

  公开号：US20040054168A1

  公开（公告）日：2004-03-18

  Disclosed herein are novel pyrrolo[2,1-c][1,4]benzodiazepine-indole derivatives of formula (I): 1 wherein each of the substituents is given the definition as set forth in the Specification and claims. Also disclosed are the preparation process of these derivatives and their uses in the manufacture of pharmaceutical compositions.

  本文披露了一种新颖的嘧啶并[2,1-c][1,4]苯二氮杂环己烯-吲哚衍生物，化学式（I）如下：其中每个取代基的定义如规范和索赔中所述。还披露了这些衍生物的制备过程以及它们在制造药物组合物中的用途。
• Thiol-based SAHA analogues as potent histone deacetylase inhibitors
  作者：Takayoshi Suzuki、Akiyasu Kouketsu、Azusa Matsuura、Arihiro Kohara、Shin-ichi Ninomiya、Kohfuku Kohda、Naoki Miyata

  DOI：10.1016/j.bmcl.2004.03.063

  日期：2004.6

  In order to find novel nonhydroxamate histone deacetylase (HDAC) inhibitors, a series of thiol-based compounds modeled after suberoylanilide hydroxamic acid (SAHA) was synthesized, and their inhibitory effect on HDACs was evaluated. Compound 6, in which the hydroxamic acid of SAHA was replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. (C) 2004 Elsevier Ltd. All rights reserved.
• US6939869B2
  申请人：——

  公开号：US6939869B2

  公开（公告）日：2005-09-06
• Novel Inhibitors of Human Histone Deacetylases:  Design, Synthesis, Enzyme Inhibition, and Cancer Cell Growth Inhibition of SAHA-Based Non-hydroxamates
  作者：Takayoshi Suzuki、Yuki Nagano、Akiyasu Kouketsu、Azusa Matsuura、Sakiko Maruyama、Mineko Kurotaki、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1021/jm049207j

  日期：2005.2.1

  To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer

  为了找到新型的非异羟肟酸酯组蛋白脱乙酰基酶（HDAC）抑制剂，设计并合成了以亚磺酰苯胺异羟肟酸（SAHA）为模型的一系列化合物。在该系列中，发现化合物7（其中SAHA的异羟肟酸被硫醇替代）与SAHA一样有效，该系列的优化导致鉴定出比SAHA更有效的HDAC抑制剂。在癌细胞生长抑制测定中，S-异丁酰基衍生物51显示出强活性，并且其效力与SAHA相当。通过Western印迹分析证实癌细胞生长抑制活性是组蛋白过度乙酰化和随后诱导p21（WAF1 / CIP1）的结果。
• Design, Synthesis, and Biological Evaluation of Pyrrolo[2,1-<i>c</i>][1,4]benzodiazepine and Indole Conjugates as Anticancer Agents
  作者：Jeh-Jeng Wang、Yu-Kai Shen、Wan-Ping Hu、Ming-Chu Hsieh、Fu-Lung Lin、Ming-Kuan Hsu、Mei-Hui Hsu

  DOI：10.1021/jm050956q

  日期：2006.2.1

  A series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) hybrids linked with indole carboxylates is described. These compounds were prepared by linking C-8 of 3 (DC-81) with an indole 2-carbonyl moiety (9) through carbon chain linkers to afford PBD hybrid agents 17-21 in good yields. Preliminary in vivo tests show that these hybrid agents have potent antitumor activity. The cytotoxic studies of the hybrid agents on human melanoma A2058 cells indicate most of the hybrids induced higher cytotoxicity, better DNA-binding ability, an increase in the apoptotic sub-G1 population, and a significant reduction in Delta Psi(mt) relative to compound 3. In addition, DNA flow cytometric analysis shows that hybrids actively induce a marked loss of cells from the G2/M phase of the cell cycle, which progresses to early apoptosis as detected by flow cytometry after double-staining with annexin V and propidium iodide (PI). Thus, we suggest that the hybrid agents are potent inducers of cell apoptosis in A2058 cells.