4-((2-(9H-pyrido[3,4-b]indole-3-carbonyl)amino)methyl)benzoic acid methyl ester | 1269418-41-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((2-(9H-pyrido[3,4-b]indole-3-carbonyl)amino)methyl)benzoic acid methyl ester
• 英文别名: methyl 4-(((9H-pyrido[3,4-b]indol-3-yl)amino)methyl)benzoate；3-(4-methoxycarbonyl-benzylamino)-β-carboline；methyl 4-[(9H-pyrido[3,4-b]indol-3-ylamino)methyl]benzoate
• CAS: 1269418-41-8
• 化学式: C₂₀H₁₇N₃O₂
• 分子量: 331.374
• InChiKey: KDTPTPWYPXIRCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  67
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((2-(9H-pyrido[3,4-b]indole-3-carbonyl)amino)methyl)benzoic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以94.6%的产率得到4-((2-(9H-pyrido[3,4-b]indole-3-carbonyl)amino)methyl)benzoic acid
  参考文献：
  名称：

  具HDAC抑制活性的β-咔啉类衍生物及制备方 法和用途

  摘要：

  本发明公开了一种具HDAC抑制活性的β-咔啉类衍生物及制备方法和用途，产品为具有通式I的化合物；可作为治疗和/或预防肝癌，结肠癌，胰腺癌，乳腺癌，肺癌，卵巢癌，膀胱癌及胃癌肿瘤药物。

  公开号：

  CN103880842B
• 作为产物：
  描述：

  3-氨基-9H-吡啶并[3,4-b]吲哚 在 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 4-((2-(9H-pyrido[3,4-b]indole-3-carbonyl)amino)methyl)benzoic acid methyl ester
  参考文献：
  名称：

  Development of novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with antiproliferative and antimetastatic activities in human cancer cells

  摘要：

  A series of novel beta-carboline-based hydroxamate derivatives 12a-k were designed and synthesized, and their biological activities in a series of in vitro assays were evaluated. Several of these beta-carboline derivatives not only showed excellent HDAC1/3/6 inhibitory effects, but also displayed significant antitumor activities against five human cancer cells. The most potent compound 12f demonstrated the highest anticancer potency against cancer cell lines with IC50 values of 0.53-1.56 mu M, which was considerably more potent than harmine (IC50 = 46.7-55.3 mu M) and also three-to ten-fold lower than that of SAHA (IC50=4.48-6.26 mu M). Immunoblot analysis revealed that 12f dose-dependently inhibited histone H3 and a-tubulin acetylation, confirming its HDAC inhibitory effects. Moreover, 12f significantly arrested HepG2 cells at G2/M phase through inhibiting cell cycle related protein CDK1 and cyclin B in a concentration dependent manner. Interestingly, 12f also exerted strong anti-metastasis activity by simultaneously reducing the protein level of MMP2 and MMP9 and inhibiting MAPK signaling pathway. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.061

文献信息

• 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.
• Development of novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with antiproliferative and antimetastatic activities in human cancer cells
  作者：Yong Ling、Jing Guo、Qiuxing Yang、Peng Zhu、Jiefei Miao、Weijie Gao、Yanfu Peng、Jiaying Yang、Kun Xu、Biao Xiong、Gongqing Liu、Jinhua Tao、Lin Luo、Qing Zhu、Yanan Zhang

  DOI：10.1016/j.ejmech.2017.12.061

  日期：2018.1

  A series of novel beta-carboline-based hydroxamate derivatives 12a-k were designed and synthesized, and their biological activities in a series of in vitro assays were evaluated. Several of these beta-carboline derivatives not only showed excellent HDAC1/3/6 inhibitory effects, but also displayed significant antitumor activities against five human cancer cells. The most potent compound 12f demonstrated the highest anticancer potency against cancer cell lines with IC50 values of 0.53-1.56 mu M, which was considerably more potent than harmine (IC50 = 46.7-55.3 mu M) and also three-to ten-fold lower than that of SAHA (IC50=4.48-6.26 mu M). Immunoblot analysis revealed that 12f dose-dependently inhibited histone H3 and a-tubulin acetylation, confirming its HDAC inhibitory effects. Moreover, 12f significantly arrested HepG2 cells at G2/M phase through inhibiting cell cycle related protein CDK1 and cyclin B in a concentration dependent manner. Interestingly, 12f also exerted strong anti-metastasis activity by simultaneously reducing the protein level of MMP2 and MMP9 and inhibiting MAPK signaling pathway. (C) 2017 Elsevier Masson SAS. All rights reserved.
• 具HDAC抑制活性的β-咔啉类衍生物及制备方 法和用途
  申请人：南通大学

  公开号：CN103880842B

  公开（公告）日：2016-04-13

  本发明公开了一种具HDAC抑制活性的β-咔啉类衍生物及制备方法和用途，产品为具有通式I的化合物；可作为治疗和/或预防肝癌，结肠癌，胰腺癌，乳腺癌，肺癌，卵巢癌，膀胱癌及胃癌肿瘤药物。