N-(cyclohexylmethyl)-9H-pyrido[3,4-b]indol-3-amine | 1269418-45-2

• 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: N-(cyclohexylmethyl)-9H-pyrido[3,4-b]indol-3-amine
• CAS: 1269418-45-2
• 化学式: C₁₈H₂₁N₃
• 分子量: 279.385
• InChiKey: GOHWRGVOLLAMEZ-UHFFFAOYSA-N

物化性质

• 熔点：
  137.0-137.8 °C
• 沸点：
  518.9±30.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  40.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-氨基-9H-吡啶并[3,4-b]吲哚 在 吡啶 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 生成 N-(cyclohexylmethyl)-9H-pyrido[3,4-b]indol-3-amine
  参考文献：
  名称：

  3-Benzylamino-β-carboline derivatives induce apoptosis through G2/M arrest in human carcinoma cells HeLa S-3

  摘要：

  beta-Carboline derivatives are known as the lead compounds for anti-tumor agents. To examine an optimal structure for anti-tumor activity, we synthesized a variety of beta-carboline derivatives, possessing a variety of substituents on the nitrogen atom of the amino group of 3-amino-beta-carboline, and evaluated their anti-tumor activity for HeLa S-3 cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MU) assay showed that an optimal structure for anti-tumor activity was 3-cyclohexylmethylamino (le) or 3-benzylamino-beta-carboline (le. An optimal counter anion of 2-methyl-3-benzylamino-beta-carbolinium salts was a triflate anion 2c. In addition, the introduction of a hydroxyl group on the meta-position of the benzyl group of 3-benzylamino-beta-carboline (3e) enhanced its anti-tumor activity. Hoechst 33342 staining and DNA fragmentation assay suggested that 1f, 2c and 3e induced cell death by apoptosis unlike le. Flow cytometry analysis showed that if, 2c and 3e induced cell apoptosis through arrest of the cell cycle in the G(2)/M phase. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.044

文献信息

• Structure-Based Design and Synthesis of N-Substituted 3-Amino-β-Carboline Derivatives as Potent αβ-Tubulin Degradation Agents
  作者：Yong Li、Yan Liu、Zejiang Zhu、Wei Yan、Chufeng Zhang、Zhuang Yang、Peng Bai、Minghai Tang、Mingsong Shi、Wen He、Suhong Fu、Jiang Liu、Kai Han、Jiewen Li、Lixin Xie、Haoyu Ye、Jianhong Yang、Lijuan Chen

  DOI：10.1021/acs.jmedchem.1c02159

  日期：2022.2.10

  So far, relatively few small molecules have been reported to promote tubulin degradation. Our previous studies have found that compound 2, a noncovalent colchicine-site ligand, was capable of promoting αβ-tubulin degradation. To further improve its antiproliferative activity, 66 derivatives or analogues of 2 were designed and synthesized based on 2-tubulin cocrystal structure. Among them, 12b displayed

  迄今为止，促进微管蛋白降解的小分子报道相对较少。我们之前的研究发现化合物2是一种非共价秋水仙碱位点配体，能够促进 αβ-微管蛋白降解。为了进一步提高其抗增殖活性，基于2-微管蛋白共晶结构，设计合成了66种2的衍生物或类似物。其中， 12b显示出针对多种肿瘤细胞的纳摩尔效力，包括紫杉醇和阿霉素耐药细胞系。 12b与秋水仙碱位点结合，并通过泛素-蛋白酶体途径以浓度依赖性方式促进 αβ-微管蛋白降解。 X射线晶体结构显示12b的结合方式与2类似，但B环的构象略有变化，这导致12b与周围残基有更好的相互作用。 12b在 A2780S（紫杉醇敏感）和 A2780T（紫杉醇耐药）卵巢异种移植模型上，静脉注射 40 mg/kg（每周 3 次）剂量均能有效抑制肿瘤生长，TGI 分别为 92.42 和 79.75%，无明显副作用。效应，支持其作为肿瘤治疗化合物的潜在用途。
• Small Molecules Promote Selective Denaturation and Degradation of Tubulin Heterodimers through a Low-Barrier Hydrogen Bond
  作者：Jianhong Yang、Yong Li、Qiang Qiu、Ruihan Wang、Wei Yan、Yamei Yu、Lu Niu、Heying Pei、Haoche Wei、Liang Ouyang、Haoyu Ye、Dingguo Xu、Yuquan Wei、Qiang Chen、Lijuan Chen

  DOI：10.1021/acs.jmedchem.2c00379

  日期：2022.7.14
• 3-Benzylamino-β-carboline derivatives induce apoptosis through G2/M arrest in human carcinoma cells HeLa S-3
  作者：Reiko Ikeda、Toshie Iwaki、Tomoko Iida、Takasumi Okabayashi、Eishiro Nishi、Masaki Kurosawa、Norio Sakai、Takeo Konakahara

  DOI：10.1016/j.ejmech.2010.11.044

  日期：2011.2

  beta-Carboline derivatives are known as the lead compounds for anti-tumor agents. To examine an optimal structure for anti-tumor activity, we synthesized a variety of beta-carboline derivatives, possessing a variety of substituents on the nitrogen atom of the amino group of 3-amino-beta-carboline, and evaluated their anti-tumor activity for HeLa S-3 cell line. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MU) assay showed that an optimal structure for anti-tumor activity was 3-cyclohexylmethylamino (le) or 3-benzylamino-beta-carboline (le. An optimal counter anion of 2-methyl-3-benzylamino-beta-carbolinium salts was a triflate anion 2c. In addition, the introduction of a hydroxyl group on the meta-position of the benzyl group of 3-benzylamino-beta-carboline (3e) enhanced its anti-tumor activity. Hoechst 33342 staining and DNA fragmentation assay suggested that 1f, 2c and 3e induced cell death by apoptosis unlike le. Flow cytometry analysis showed that if, 2c and 3e induced cell apoptosis through arrest of the cell cycle in the G(2)/M phase. (C) 2010 Elsevier Masson SAS. All rights reserved.