N-(9H-β-carbolin-3-yl)acetamide | 91985-75-0

• 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-(9H-β-carbolin-3-yl)acetamide
• 英文别名: 3-(acetylamino)-β-carboline；N-9h-pyrido[3,4-b]indol-3-yl-acetamide；N-(9H-pyrido[3,4-b]indol-3-yl)acetamide
• CAS: 91985-75-0
• 化学式: C₁₃H₁₁N₃O
• 分子量: 225.25
• InChiKey: JZIFOHJMLBAWQZ-UHFFFAOYSA-N

物化性质

• 熔点：
  206 °C
• 沸点：
  573.3±30.0 °C(Predicted)
• 密度：
  1.387±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  57.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(9H-β-carbolin-3-yl)acetamide 在 盐酸 、 sodium nitrate 、 溶剂黄146 、 三氟乙酸 作用下， 以 甲醇 、 水 为溶剂， 反应 34.0h， 生成
  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 、 氯化亚砜 、 三氯异氰尿酸 、 一水合肼 、 溶剂黄146 、 三乙胺 、 sodium nitrite 作用下， 以 戊醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 N-(9H-β-carbolin-3-yl)acetamide
  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

• .beta.-carbolines and their use as tranquilizers
  申请人：Schering Aktiengesellschaft

  公开号：US04731358A1

  公开（公告）日：1988-03-15

  New substituted .beta.-carbolines of formula I ##STR1## wherein R.sup.3 is hydrogen or a non-carboxyl based substituent, and R.sup.4-9 have various meanings, are valuable pharmaceutical products with long lasting action on the central nervous system.

  公式I中的新取代的β-咔啉化合物 ##STR1## 其中R.sup.3是氢或非羧基取代基，而R.sup.4-9具有不同的含义，是具有中枢神经系统长效作用的有价值的药物产品。
• 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.
• 3-Amino-.beta.-carboline derivatives and the benzodiazepine receptor. Synthesis of a selective antagonist of the sedative action of diazepam
  作者：Robert H. Dodd、Catherine Ouannes、Lia Prado de Carvalho、Anne Valin、Patrice Venault、Georges Chapouthier、Jean Rossier、Pierre Potier

  DOI：10.1021/jm00383a024

  日期：1985.6

  Seven 3-N-substituted derivatives of 3-amino-beta-carboline were synthesized and their affinities for the benzodiazepine receptor were assessed in vitro. Two compounds, 3-(ethylamino)-beta-carboline and 3-[(methoxycarbonyl)amino]-beta-carboline (beta-CMC), showing IC50 values of 460 and 71 nM, respectively, were selected for in vivo studies. The former compound showed long-lasting proconvulsant activity in Papio papio baboons while beta-CMC was shown in mice to selectively antagonize the sedative effects of diazepam without exhibiting convulsant, proconvulsant, or anxiogenic activity by itself.
• DODD, R. H.;OUANNES, C.;CARVALHO, L. P. DE;VALIN, A.;VENAULT, P.;CHAPOUTH+, J. MED. CHEM., 1985, 28, N 6, 824-828
  作者：DODD, R. H.、OUANNES, C.、CARVALHO, L. P. DE、VALIN, A.、VENAULT, P.、CHAPOUTH+

  DOI：——

  日期：——
• US4731358A
  申请人：——

  公开号：US4731358A

  公开（公告）日：1988-03-15