8-amino-3-benzylamino-6-chloro-9H-β-carboline | 1376918-13-6

• 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: 8-amino-3-benzylamino-6-chloro-9H-β-carboline
• 英文别名: 3-N-benzyl-6-chloro-9H-pyrido[3,4-b]indole-3,8-diamine
• CAS: 1376918-13-6
• 化学式: C₁₈H₁₅ClN₄
• 分子量: 322.797
• InChiKey: WBMXOGFEELVCJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  66.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-amino-3-benzylamino-6-chloro-9H-β-carboline 在 sodium tetrahydroborate 、 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 3-benzylamino-6-chloro-8-methylamino-9H-β-carboline
  参考文献：
  名称：

  Structure–activity relationship in the antitumor activity of 6-, 8- or 6,8-substituted 3-benzylamino-β-carboline derivatives

  摘要：

  We synthesized 47 kinds of 3-amino- or 3-benzylamino-beta-carboline derivatives with a substituent on the 6-, 8-, or 6,8-carbon atoms and evaluated their antitumor activities for Hela S-3 and Sarcoma 180 cell lines using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Consequently, we succeeded to develop 3-benzylamino-8-methylamino-beta-carboline (17a) and 8-methylamino-3-(3-phenoxybenzyl)amino-beta-carboline (17c) with antitumor activity with IC50 values of 0.046, 0.032 mu M, respectively, against HeLa S-3 cell line, which are higher than that of previously reported 3-(3-phenoxybenzyl)amino-beta-carboline (10e) of 0.074 mu M. Furthermore, effects of Cl group at 6-carbon atom on the type of cell death was evaluated using 3-benzylamino-6-chloro-beta-carboline (10b), 3-benzylamino-beta-carboline (10d), N-(3-benzylamino)-6-chloro-9H-beta-carbolin-8-yl)benzamide (14g), and N-(3-benzylamino-9H-beta-carbolin-8-yl)benzamide (17b) to show no effect. Hoechst 33342 staining and DNA fragmentation assay suggested that these compounds induced cell death by apoptosis. In addition, using flow cytometry analysis, we established that the cell death pathway was through the arrest of the cell cycle in the G(2)/M phase. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.077
• 作为产物：
  描述：

  (S)-2,3,4,9-四氢-1H-吡啶[3,4-b]吲哚-3-羧酸 在 盐酸 、 sodium nitrate 、 N-氯代丁二酰亚胺 、 氯化亚砜 、 tin(II) chloride dihdyrate 、 三氯异氰尿酸 、 sodium cyanoborohydride 、 一水合肼 、 溶剂黄146 、 三乙胺 、 三氟乙酸 、 sodium nitrite 作用下， 以 甲醇 、 戊醇 、 氯仿 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 137.5h， 生成 8-amino-3-benzylamino-6-chloro-9H-β-carboline
  参考文献：
  名称：

  Structure–activity relationship in the antitumor activity of 6-, 8- or 6,8-substituted 3-benzylamino-β-carboline derivatives

  摘要：

  We synthesized 47 kinds of 3-amino- or 3-benzylamino-beta-carboline derivatives with a substituent on the 6-, 8-, or 6,8-carbon atoms and evaluated their antitumor activities for Hela S-3 and Sarcoma 180 cell lines using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Consequently, we succeeded to develop 3-benzylamino-8-methylamino-beta-carboline (17a) and 8-methylamino-3-(3-phenoxybenzyl)amino-beta-carboline (17c) with antitumor activity with IC50 values of 0.046, 0.032 mu M, respectively, against HeLa S-3 cell line, which are higher than that of previously reported 3-(3-phenoxybenzyl)amino-beta-carboline (10e) of 0.074 mu M. Furthermore, effects of Cl group at 6-carbon atom on the type of cell death was evaluated using 3-benzylamino-6-chloro-beta-carboline (10b), 3-benzylamino-beta-carboline (10d), N-(3-benzylamino)-6-chloro-9H-beta-carbolin-8-yl)benzamide (14g), and N-(3-benzylamino-9H-beta-carbolin-8-yl)benzamide (17b) to show no effect. Hoechst 33342 staining and DNA fragmentation assay suggested that these compounds induced cell death by apoptosis. In addition, using flow cytometry analysis, we established that the cell death pathway was through the arrest of the cell cycle in the G(2)/M phase. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.077

文献信息

• Structure–activity relationship in the antitumor activity of 6-, 8- or 6,8-substituted 3-benzylamino-β-carboline derivatives
  作者：Reiko Ikeda、Takanori Kimura、Tatsuya Tsutsumi、Syunsuke Tamura、Norio Sakai、Takeo Konakahara

  DOI：10.1016/j.bmcl.2012.03.077

  日期：2012.5

  We synthesized 47 kinds of 3-amino- or 3-benzylamino-beta-carboline derivatives with a substituent on the 6-, 8-, or 6,8-carbon atoms and evaluated their antitumor activities for Hela S-3 and Sarcoma 180 cell lines using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Consequently, we succeeded to develop 3-benzylamino-8-methylamino-beta-carboline (17a) and 8-methylamino-3-(3-phenoxybenzyl)amino-beta-carboline (17c) with antitumor activity with IC50 values of 0.046, 0.032 mu M, respectively, against HeLa S-3 cell line, which are higher than that of previously reported 3-(3-phenoxybenzyl)amino-beta-carboline (10e) of 0.074 mu M. Furthermore, effects of Cl group at 6-carbon atom on the type of cell death was evaluated using 3-benzylamino-6-chloro-beta-carboline (10b), 3-benzylamino-beta-carboline (10d), N-(3-benzylamino)-6-chloro-9H-beta-carbolin-8-yl)benzamide (14g), and N-(3-benzylamino-9H-beta-carbolin-8-yl)benzamide (17b) to show no effect. Hoechst 33342 staining and DNA fragmentation assay suggested that these compounds induced cell death by apoptosis. In addition, using flow cytometry analysis, we established that the cell death pathway was through the arrest of the cell cycle in the G(2)/M phase. (C) 2012 Elsevier Ltd. All rights reserved.