[3-(4-fluorophenyl)-6-methyl-6,11-dihydro-5H-indolizino [6,7-b]indole-1,2-diyl]bis(methylene)bis(ethylcarbamate) | 1422377-15-8

• 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: [3-(4-fluorophenyl)-6-methyl-6,11-dihydro-5H-indolizino [6,7-b]indole-1,2-diyl]bis(methylene)bis(ethylcarbamate)
• 英文别名: [3-(4-fluorophenyl)-6-methyl-6,11-dihydro-5H-indolizino[6,7-b]indole-1,2-diyl]bis(methylene) bis(ethylcarbamate)；BO-1918；[2-(ethylcarbamoyloxymethyl)-1-(4-fluorophenyl)-9-methyl-4,10-dihydroindolizino[6,7-b]indol-3-yl]methyl N-ethylcarbamate
• CAS: 1422377-15-8
• 化学式: C₂₉H₃₁FN₄O₄
• 分子量: 518.588
• InChiKey: XBTFUOSKUIKOGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  86.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl (3S)-1,2,3,4-tetrahydro-β-carboline-3-carboxylate 在 lithium aluminium tetrahydride 、 乙酸酐 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 mineral oil 为溶剂， 反应 18.75h， 生成 [3-(4-fluorophenyl)-6-methyl-6,11-dihydro-5H-indolizino [6,7-b]indole-1,2-diyl]bis(methylene)bis(ethylcarbamate)
  参考文献：
  名称：

  Novel Antitumor Indolizino[6,7-b]indoles with Multiple Modes of Action: DNA Cross-Linking and Topoisomerase I and II Inhibition

  摘要：

  A series of bis(hydroxymethyl)indolizino[6,7-b]indoles and their bis(alkylcarbamates) were synthesized for antitumor studies. These agents were designed as hybrid molecules of beta-carboline (topoisomerase inhibition moiety) and bis(hydroxymethyl)pyrrole (DNA cross-linking moiety). The preliminary antitumor studies indicated that these agents exhibited significant cytotoxicity against a variety of human tumor cells in vitro. Treatment of human breast carcinoma MX-1 xenograft-bearing nude mice with compounds 18b and 28c achieved more than 99% tumor remission. We also observed that 18a displayed potent therapeutic efficacy against human lung adenocarcinoma A549 and colon cancer HT 29 xenografts. These results revealed that compound 18a was more potent than irinotecan against HT 29 cells and was as potent as irinotecan against A549 cells in xenograft models. Furthermore, we demonstrated that these derivatives possess multiple modes of action, such as induction of DNA cross-linking, inhibition of topoisomerase I and II, and cell-cycle arrest at the S-phase.

  DOI：

  10.1021/jm301788a

文献信息

• METHODS FOR TREATING SMALL CELL LUNG CANCERS BY USING PHARMACEUTICAL COMPOSITIONS OR COMBINATIONS COMPRISING INDOLIZINO[6,7-B]INDOLE DERIVATIVES
  申请人：SU Tsann-Long

  公开号：US20190247371A1

  公开（公告）日：2019-08-15

  A method for treating small cell lung cancer (SCLC). In the method, a therapeutically effective amount of a compound of Formula I: wherein R 1 , R 2 and R 3 have the definitions disclosed in the specification is administered alone or in combination with one or more anticancer agents, or surgery, radiation therapy, chemotherapy, and/or targeted therapy.
• US8703951B2
  申请人：——

  公开号：US8703951B2

  公开（公告）日：2014-04-22
• Novel Antitumor Indolizino[6,7-<i>b</i>]indoles with Multiple Modes of Action: DNA Cross-Linking and Topoisomerase I and II Inhibition
  作者：Ravi Chaniyara、Satishkumar Tala、Chi-Wei Chen、Xiuguo Zang、Rajesh Kakadiya、Li-Fang Lin、Ching-Huang Chen、Shin-I Chien、Ting-Chao Chou、Tung-Hu Tsai、Te-Chang Lee、Anamik Shah、Tsann-Long Su

  DOI：10.1021/jm301788a

  日期：2013.2.28

  A series of bis(hydroxymethyl)indolizino[6,7-b]indoles and their bis(alkylcarbamates) were synthesized for antitumor studies. These agents were designed as hybrid molecules of beta-carboline (topoisomerase inhibition moiety) and bis(hydroxymethyl)pyrrole (DNA cross-linking moiety). The preliminary antitumor studies indicated that these agents exhibited significant cytotoxicity against a variety of human tumor cells in vitro. Treatment of human breast carcinoma MX-1 xenograft-bearing nude mice with compounds 18b and 28c achieved more than 99% tumor remission. We also observed that 18a displayed potent therapeutic efficacy against human lung adenocarcinoma A549 and colon cancer HT 29 xenografts. These results revealed that compound 18a was more potent than irinotecan against HT 29 cells and was as potent as irinotecan against A549 cells in xenograft models. Furthermore, we demonstrated that these derivatives possess multiple modes of action, such as induction of DNA cross-linking, inhibition of topoisomerase I and II, and cell-cycle arrest at the S-phase.