NSC 317605 | 34374-22-6

• 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: NSC 317605
• 英文别名: (3-chloro-8-methoxy-11H-indolo[3,2-c]quinolin-9-ylmethyl)-diethyl-amine；3-Chloro-8-methoxy-9-diaethylaminomethyl-11H-indolo<3,2-c>chinolin；11H-Indolo[3,2-c]quinolin-9-amine, 3-chloro-N,N-diethyl-8-methoxy-；N-[(3-chloro-8-methoxy-11H-indolo[3,2-c]quinolin-9-yl)methyl]-N-ethylethanamine
• CAS: 34374-22-6
• 化学式: C₂₁H₂₂ClN₃O
• 分子量: 367.878
• InChiKey: LLEAEDYSPVHUEP-UHFFFAOYSA-N

物化性质

• 沸点：
  549.0±45.0 °C(Predicted)
• 密度：
  1.273±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  41.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-二乙氨基-1-溴乙烷氢溴酸盐 、 NSC 317605 在 sodium hydroxide 、 苄基三乙基氯化铵 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以25%的产率得到3-Chloro-9-[[diethylamino]methyl]-N,N-diethyl-8-methoxy-11H-indolo[3,2-c]quinoline
  参考文献：
  名称：

  Structure-activity relationships of antimalarial indolo[3,2-c]quinolines [1, 2]

  摘要：

  Structure-activity relationships have been ascertained and chemical methodology developed for a series of antimalarial 3-chloroindolo[3,2-c]quinoline-5-oxides. The basic side chain as well as the ring N-oxide are critical for antimalarial activity as is a bromine or chlorine in position 3. Substitution at positions 7, 8, 9, 10 is not essential, although the most potent analog in our studies was the 8-nitro compound 4vv.

  DOI：

  10.1016/0223-5234(93)90036-e
• 作为产物：
  描述：

  methyl N-(3-chlorophenyl)-β-alaninate 在 吡啶 、 盐酸 、 PPA 作用下， 以 1,4-二氧六环 、 异丙醇 为溶剂， 反应 65.33h， 生成 NSC 317605
  参考文献：
  名称：

  Structure-activity relationships of antimalarial indolo[3,2-c]quinolines [1, 2]

  摘要：

  Structure-activity relationships have been ascertained and chemical methodology developed for a series of antimalarial 3-chloroindolo[3,2-c]quinoline-5-oxides. The basic side chain as well as the ring N-oxide are critical for antimalarial activity as is a bromine or chlorine in position 3. Substitution at positions 7, 8, 9, 10 is not essential, although the most potent analog in our studies was the 8-nitro compound 4vv.

  DOI：

  10.1016/0223-5234(93)90036-e

文献信息

• Indoloquinoline-Mediated Targeted Downregulation of KRAS through Selective Stabilization of the Mid-Promoter G-Quadruplex Structure
  作者：Alexandra Maria Psaras、Rhianna K. Carty、Jared T. Miller、L. Nathan Tumey、Tracy A. Brooks

  DOI：10.3390/genes13081440

  日期：——

  KRAS is a well-validated anti-cancer therapeutic target, whose transcriptional downregulation has been demonstrated to be lethal to tumor cells with aberrant KRAS signaling. G-quadruplexes (G4s) are non-canonical nucleic acid structures that mediate central dogmatic events, such as DNA repair, telomere elongation, transcription and splicing events. G4s are attractive drug targets, as they are more globular than B-DNA, enabling more selective gene interactions. Moreover, their genomic prevalence is increased in oncogenic promoters, their formation is increased in human cancers, and they can be modulated with small molecules or targeted nucleic acids. The putative formation of multiple G4s has been described in the literature, but compounds with selectivity among these structures have not yet been able to distinguish between the biological contribution of the predominant structures. Using cell free screening techniques, synthesis of novel indoloquinoline compounds and cellular models of KRAS-dependent cancer cells, we describe compounds that choose between KRAS promoter G4near and G4mid, correlate compound cytotoxic activity with KRAS regulation, and highlight G4mid as the lead molecular non-canonical structure for further targeting efforts.

  KRAS 是一个有效的抗癌治疗靶点，其转录下调对 KRAS 信号异常的肿瘤细胞具有致死作用。G 型四聚体（G4s）是一种非经典核酸结构，可介导 DNA 修复、端粒伸长、转录和剪接等中心事件。G4s 是有吸引力的药物靶点，因为它们比 B-DNA 更为球状，能够进行更有选择性的基因相互作用。此外，它们在致癌启动子中的基因组普遍存在，在人类癌症中的形成也有所增加，而且可以用小分子或靶向核酸对它们进行调节。文献中已经描述了多种 G4 的推定形成，但在这些结构中具有选择性的化合物尚未能区分主要结构的生物贡献。利用无细胞筛选技术、新型吲哚喹啉化合物的合成以及 KRAS 依赖性癌细胞模型，我们描述了在 KRAS 启动子 G4near 和 G4mid 之间进行选择的化合物，将化合物的细胞毒性活性与 KRAS 调节联系起来，并强调 G4mid 是进一步靶向研究的主要非经典分子结构。
• Werbel L. M., Kesten S. J., Turner W. R., Eur. J. Med. Chem, 28 (1993) N 11, S 837-852
  作者：Werbel L. M., Kesten S. J., Turner W. R.

  DOI：——

  日期：——
• IBRAHIM, EL-SAYED;MONTGOMERIE, ANITA M.;SNEDDON, ANDREW H.;PROCTOR, GEORG+, EUR. J. MED. CHEM., 23,(1988) N 2, 183-188
  作者：IBRAHIM, EL-SAYED、MONTGOMERIE, ANITA M.、SNEDDON, ANDREW H.、PROCTOR, GEORG+

  DOI：——

  日期：——
• Structure-activity relationships of antimalarial indolo[3,2-c]quinolines [1, 2]
  作者：LM Werbel、SJ Kesten、WR Turner

  DOI：10.1016/0223-5234(93)90036-e

  日期：1993.1

  Structure-activity relationships have been ascertained and chemical methodology developed for a series of antimalarial 3-chloroindolo[3,2-c]quinoline-5-oxides. The basic side chain as well as the ring N-oxide are critical for antimalarial activity as is a bromine or chlorine in position 3. Substitution at positions 7, 8, 9, 10 is not essential, although the most potent analog in our studies was the 8-nitro compound 4vv.