6-oxo-6H-indeno[2,1-b]quinoline-4-carboxylic acid | 191172-59-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-oxo-6H-indeno[2,1-b]quinoline-4-carboxylic acid
• 英文别名: 6-Oxoindeno[2,1-b]quinoline-4-carboxylic acid
• CAS: 191172-59-5
• 化学式: C₁₇H₉NO₃
• 分子量: 275.263
• InChiKey: CSKIUYOGWQOZQX-UHFFFAOYSA-N

物化性质

• 沸点：
  570.1±30.0 °C(Predicted)
• 密度：
  1.490±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 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：
  67.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-oxo-6H-indeno[2,1-b]quinoline-4-carboxylic acid 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-[2-(dimethylamino)ethyl]-6-oxoindeno[2,1-b]quinoline-4-carboxamide
  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：

  苯丙酮酸 在 sodium hydroxide 、 PPA 作用下， 以 乙醇 为溶剂， 反应 17.0h， 生成 6-oxo-6H-indeno[2,1-b]quinoline-4-carboxylic acid
  参考文献：
  名称：

  摘要：

  The acid precursors of the title compounds were prepared from methyl 2-amino-3-formylbenzoate (3), by Friedlander synthesis with o-methoxy- and o-nitro-phenylacetic acids, phenylpyruvic acid and benzo[b]thiophen-2-one, respectively. Except for the last example, cyclization of an initial 3-arylquinoline derivative was then required to give the tetracycle. Growth inhibition properties of the carboxamides in a series of cancer cell lines were measured for comparison with previous data for an isomeric series. In all cases, the present set were found to be less active.

  DOI：

  10.1071/ch99166

文献信息

• Synthesis and antitumor activity of some indeno[1,2- b ]quinoline-based bis carboxamides
  作者：Leslie W Deady、José Desneves、Anthony J Kaye、Graeme J Finlay、Bruce C Baguley、William A Denny

  DOI：10.1016/s0968-0896(00)00039-0

  日期：2000.5

  A series of bis(11-oxo-1 1H-indeno[1,2-b]quinoline-6-carboxamides) linked through the B-carboxamides were prepared by coupling the requisite acid imidazolides with Various diamines. Compounds with mono-cationic linker chains were more potent cytotoxins than the corresponding monomer in a panel of rodent and human cell lines: while those with the dicationic linker chains (CH2)(2)NR(CH2)(2)NR(CH2)(2) and (CH2)(2)NR(CH2)(3)NR(CH2)(2) showed extraordinarily high potencies (for example, IC(50)s of 0.18-1.4 nM against human Jurkat leukemia; up to 1000-fold more potent than the parent monomer). As seen previously in the monomeric series, small, lipophilic 4-substituents significantly increased potency in cell culture. The dimeric compounds were all slightly to significantly more potent in the mutant JL(A) and JL(D) cell lines that under-express topo II, suggesting that this enzyme is not their primary target. An Il-imino-linked dimer was much less active, and an asymmetric indeno[1,2-b]quinoline-6-carboxamide/naphthalimide dimer was less active than the comparable symmetric bis(indeno[1,2-b]quinoline-6-carboxamide). Selected analogues were active against sub-cutaneously implanted colon 38 tumors in mice? giving growth delays comparable to that of the clinical topo I inhibitor irinotecan at up to 10-fold lower doses. These compounds form an interesting new class of putative topo I inhibitors. (C) 2000 Elsevier Science Ltd. 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。
• ——
  作者：Xianyong Bu、Leslie W. Deady、William A. Denny

  DOI：10.1071/ch99166

  日期：——

  The acid precursors of the title compounds were prepared from methyl 2-amino-3-formylbenzoate (3), by Friedlander synthesis with o-methoxy- and o-nitro-phenylacetic acids, phenylpyruvic acid and benzo[b]thiophen-2-one, respectively. Except for the last example, cyclization of an initial 3-arylquinoline derivative was then required to give the tetracycle. Growth inhibition properties of the carboxamides in a series of cancer cell lines were measured for comparison with previous data for an isomeric series. In all cases, the present set were found to be less active.