N-[2-(dimethylamino)ethyl]-11-oxoindeno[1,2-b]quinoline-6-carboxamide | 191172-32-4

• 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: N-[2-(dimethylamino)ethyl]-11-oxoindeno[1,2-b]quinoline-6-carboxamide
• CAS: 191172-32-4
• 化学式: C₂₁H₁₉N₃O₂
• 分子量: 345.401
• InChiKey: MBTIJGXSMFLPAV-UHFFFAOYSA-N

物化性质

• 沸点：
  621.4±45.0 °C(Predicted)
• 密度：
  1.282±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  O,O'-1,6-hexanediylbishydroxylamine dihydrochloride 、 N-[2-(dimethylamino)ethyl]-11-oxoindeno[1,2-b]quinoline-6-carboxamide 在 盐酸 作用下， 反应 3.0h， 以84%的产率得到11,11'-[(O,O'-hexane-1,6-diyl)bisisonitroso]bis-[N-[2-(dimethylamino)ethyl]-11H-indeno[1,2-b]quinoline-6-carboxamide]
  参考文献：
  名称：

  Synthesis and antitumor activity of some indeno[1,2- b ]quinoline-based bis carboxamides

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(00)00039-0
• 作为产物：
  描述：

  4-Methyl-10H-indeno<1,2-b>quinoline 在 chromium(VI) oxide 、 硫酸 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸酐 、 溶剂黄146 为溶剂， 反应 3.0h， 生成 N-[2-(dimethylamino)ethyl]-11-oxoindeno[1,2-b]quinoline-6-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

文献信息

• Ring-substituted 11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides with similar patterns of cytotoxicity to the dual topo I/II inhibitor DACA
  作者：Leslie W. Deady、José Desneves、Anthony J. Kaye、Michelle Thompson、Graeme J. Finlay、Bruce C. Baguley、William A. Denny

  DOI：10.1016/s0968-0896(99)00231-x

  日期：1999.12

  A series of ring-substituted analogues of the topoisomerase inhibitor 11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides was prepared and evaluated. The compounds were prepared by Pfitzinger reaction of the appropriate isatin-7-carboxylic acids and 1-indanones, followed by selective thermal decarboxylation of the resulting tetracyclic diacids, subsequent oxidation of the methylene group with alkaline permanganate under carefully controlled conditions, and 1,1'-carbonyldiimidazole-induced amidation. The compounds were evaluated in a panel of cell lines in culture. The largest increases in cytotoxicity (five to tenfold) were shown by 4-substituted analogues, with the 4-Cl derivative having an IC50 of 8 nM against the Lewis lung carcinoma. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Positioning of the Carboxamide Side Chain in 11-Oxo-11 H -indeno[1,2- b ]quinolinecarboxamide Anticancer Agents: Effects on Cytotoxicity
  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)00264-9

  日期：2001.2

  A series of 11-oxo-11H-indeno[1,2-b]quinolines bearing a carboxamide-linked cationic side chain at various positions on the chromophore was studied to determine structure-activity relationships between cytotoxicity and the position of the side chain. The compounds were prepared by Pfitzinger synthesis from an appropriate isatin and 1-indanone, followed by various oxidative steps, to generate the required carboxylic acids. The 4- and 6-carboxamides (with the side chain on a terminal ring, off the short axis of the chromophore) were effective cytotoxins. The dimeric 4- and 6-linked analogues were considerably more cytotoxic than the parent monomers, but had broadly similar activities. In contrast, analogues with side chains at the 8-position ton a terminal ring but off the long axis of the chromophore) or 10-position (off the short axis of the chromophore but in a central ring) were drastically less effective. The 4,10- and 6,10-biscarboxamides had activities between those of the corresponding parent monocarboxamides. The first of these showed good activity against advanced subcutaneous colon 38 tumours in mice. (C) 2001 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。
• 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.