11H-11-oxoindeno<1,2-b>quinoxaline-6-carboxylic acid | 154458-02-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 11H-11-oxoindeno<1,2-b>quinoxaline-6-carboxylic acid
• 英文别名: 11-oxo-11H-indeno<1,2-b>quinoxaline-6-carboxylic acid；11H-indeno[1,2-b]quinoxalin-11-one-6-carboxylic acid；11-oxo-11H-indeno[1,2-b]quinoxaline-6-carboxylic acid；11-Oxoindeno[2,1-b]quinoxaline-6-carboxylic acid；11-oxoindeno[2,1-b]quinoxaline-6-carboxylic acid
• CAS: 154458-02-3
• 化学式: C₁₆H₈N₂O₃
• 分子量: 276.251
• InChiKey: GALJTJMFUJPTOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  11H-11-oxoindeno<1,2-b>quinoxaline-6-carboxylic acid 在 氢氧化钾 、 一水合肼 、 三乙胺 作用下， 以 二氯甲烷 、 乙二醇 为溶剂， 反应 9.0h， 生成 11H-Indeno[1,2-b]quinoxaline-6-carboxylic acid (2-dimethylamino-ethyl)-amide
  参考文献：
  名称：

  稠合四环喹啉和喹喔啉的N- [2-（二甲基氨基）乙基]羧酰胺衍生物的合成及其抗肿瘤特性：一类新型的拓扑异构酶抑制剂。

  摘要：

  制备了一系列四环喹啉和喹喔啉羧酰胺，并在一系列鼠类人肿瘤细胞系中评估了它们的细胞毒性。多数喹啉衍生物是通过适应Pfitzinger合成，随后进行热脱羧并使用氯甲酸异丁酯通过混合酸酐法与N，N-二甲基乙二胺偶联而制备的。喹啉类似物显示出与已知的三环a啶-4-羧酰胺混合的topoI / II抑制剂DACA相似的细胞毒性，其中噻吩和茚满类似物最具活性。他们显示出对Jurkat人白血病topo II耐药株JLA和JLC的效力几乎没有降低，表明它们的细胞毒性并非主要是由于对topo II的抑制所致。喹喔啉类似物的IC50值变化更大，与喹啉衍生物相比，其平均细胞毒性要低，但似乎具有相似的作用方式。总的来说，这类新化合物似乎是混合的topo I / II抑制剂，在研究的人类白血病细胞系中的细胞毒性比DACA高三倍，在结肠38的体内活性与DACA和阿霉素相当。

  DOI：

  10.1021/jm970044r
• 作为产物：
  描述：

  2,3-二氨基甲苯 在 chromium(VI) oxide 、 硫酸 、 乙酸酐 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 0.58h， 生成 11H-11-oxoindeno<1,2-b>quinoxaline-6-carboxylic acid
  参考文献：
  名称：

  Synthesis of some 11H-indeno[1,2-b]quinoxalin-11-ones

  摘要：

  Condensation of substituted o-phenylene diamines and ninhydrins gave the tide compounds. The substituent orientation in the products was determined by H-1 NMR analysis of the chemical shifts brought about by N5-oxidation. Reduction of the 8-nitro to 8-amino compound was achieved both with and without reduction of the carbonyl group. Nitration of the 8-carboxylic acid occurred in the 2-position.

  DOI：

  10.1016/s0040-4020(01)80184-8

文献信息

• Discovery of indeno[1,2- b ]quinoxaline derivatives as potential anticancer agents
  作者：Chih-Hua Tseng、You-Ren Chen、Cherng-Chyi Tzeng、Wangta Liu、Chon-Kit Chou、Chien-Chih Chiu、Yeh-Long Chen

  DOI：10.1016/j.ejmech.2015.11.031

  日期：2016.1

  We have synthesized certain indeno[1,2-b]quinoxaline derivatives for antiproliferative evaluation. Among them, 11-[3-(dimethylamino)propoxy]imino}-N-[3-(dimethylamino) propyl]-11H-indeno(1,2-b] quinoxaline-6-carboxamide (10a) was active against the growth of MDA-MB231, PC-3, and Huh-7 with IC50 values of 0.87 (selectivity index, SI = 36.22), 0.82 (SI = 38.43), and 0.64 mu M (SI = 49.23) respectively. Compound 10a was inactive against the growth of normal human fetal lung fibroblast cell line (MRC-5) with an IC50 value of 31.51 mu M. Its analogs, 10b and 10c, were also active against the growth of MB231, PC-3, and Huh-7 with IC50 values of <1.0.mu M in each case. Our results have also indicated compounds 10a-10c exhibited comparable inhibitory activities against topo I and topo II with the positive compound 2 at a concentration of 10 mu M. Mechanism studies indicated that compound 10a induced cell cycle arrest at S phase via activation of caspase-3, -7 and an increase in the protein expression of Bad and Bax but a decrease in expression of Bcl-2 and PARP, which consequently cause cell death. In addition, compound 10a attenuated the levels of phosphorylated Src, Akt-1, and Akt-2 protein levels but did not affect the total protein expression of Akt. We have also implanted human hepatocellular carcinoma cells into the yolk sac of zebrafish larvae and incubated larvae with various concentrations of 10a. Our results of the zebrafish xenograft assay confirmed the anti-tumor effect of 10a in vivo. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Synthesis and Antitumor Properties of <i>N</i>-[2-(Dimethylamino)ethyl]carboxamide Derivatives of Fused Tetracyclic Quinolines and Quinoxalines:  A New Class of Putative Topoisomerase Inhibitors
  作者：Leslie W. Deady、Anthony J. Kaye、Graeme J. Finlay、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm970044r

  日期：1997.6.1

  does not result primarily from inhibition of topo II. The quinoxaline analogues had more varied IC50 values, being on average less cytotoxic than the quinoline derivatives, but appeared to have a similar mode of action. Overall, this new class of compounds appear to be mixed topo I/II inhibitors, up to 3-fold more cytotoxic than DACA in the human leukemia cell lines studied, with in vivo activity in

  制备了一系列四环喹啉和喹喔啉羧酰胺，并在一系列鼠类人肿瘤细胞系中评估了它们的细胞毒性。多数喹啉衍生物是通过适应Pfitzinger合成，随后进行热脱羧并使用氯甲酸异丁酯通过混合酸酐法与N，N-二甲基乙二胺偶联而制备的。喹啉类似物显示出与已知的三环a啶-4-羧酰胺混合的topoI / II抑制剂DACA相似的细胞毒性，其中噻吩和茚满类似物最具活性。他们显示出对Jurkat人白血病topo II耐药株JLA和JLC的效力几乎没有降低，表明它们的细胞毒性并非主要是由于对topo II的抑制所致。喹喔啉类似物的IC50值变化更大，与喹啉衍生物相比，其平均细胞毒性要低，但似乎具有相似的作用方式。总的来说，这类新化合物似乎是混合的topo I / II抑制剂，在研究的人类白血病细胞系中的细胞毒性比DACA高三倍，在结肠38的体内活性与DACA和阿霉素相当。
• Synthesis of some 11H-indeno[1,2-b]quinoxalin-11-ones
  作者：Leslie W Deady、José Desneves、Andrew C Ross

  DOI：10.1016/s0040-4020(01)80184-8

  日期：1993.1

  Condensation of substituted o-phenylene diamines and ninhydrins gave the tide compounds. The substituent orientation in the products was determined by H-1 NMR analysis of the chemical shifts brought about by N5-oxidation. Reduction of the 8-nitro to 8-amino compound was achieved both with and without reduction of the carbonyl group. Nitration of the 8-carboxylic acid occurred in the 2-position.