6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline

• 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-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline
• 英文别名: N'-[6-methoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]propane-1,3-diamine
• 化学式: C₂₁H₂₂F₃N₃O₂
• 分子量: 405.42
• InChiKey: PPRRJSWOEFBRDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  69.4
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline 、 丁二酸 以 甲醇 为溶剂， 以100%的产率得到6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline succinate
  参考文献：
  名称：

  Synthesis and anti-breast cancer activities of substituted quinolines

  摘要：

  Promising anti-breast cancer agents derived from substituted quinolines were discovered. The quinolines were readily synthesized in a large scale from a sequence of reactions starting from 4-acetamidoanisole. The Michael addition product was isolated as the reaction intermediate in the ring closing reaction of 4-amino-5-nitro-2-(3-trifluoromethylphenyloxy) anisole with methyl vinyl ketone leading to 6-methoxy-4-methyl-8-nitro-5-(3-trifluoromethylphenyloxy) quinoline (14). The amino function of 8-amino-6-methoxy-4- methyl-5-(3-trifluoromethylphenyloxy) quinoline, prepared from 14, was connected to various side chains via alkylation with N( 3-iodopropyl) phthalimide, Michael addition with acrylonitrile, and reductive amination with various heterocycle carboxaldehydes, such as imidazole-4-carboxaldehyde, thiophene-2-carboxaldehyde, and 2-furaldehyde. Effects of the substituted quinolines on cell viability of T47D breast cancer cells using trypan blue exclusion assay were examined. The results showed that the IC50 value of 6-methoxy-8-[(2-furanylmethyl) amino]-4-methyl-5-(3-trifluoromethylphenyloxy) quinoline is 16 +/- 3 nM, the lowest IC50 out of all the quinolines tested. IC50 values of three other quinolines are in the nanomolar range, a desirable range for pharmacological testing. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.04.024
• 作为产物：
  描述：

  6-methoxy-8-(3-phthalimidopropylamino)-4-methyl-5-(3-trifluoromethylphenyloxy)-quinoline 在 氩 、 二氯甲烷 、 Brine 、 potassium carbonate 、 silica gel 作用下， 以 肼 、 乙醇 、 氢氧化钾 为溶剂， 反应 3.0h， 以to give 1.86 g (80% yield) of 6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline的产率得到6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline
  参考文献：
  名称：

  COMPOUNDS AFFECTING GAP JUNCTION ACTIVITY

  摘要：

  本发明涉及新型喹啉化合物，其影响间隙连接活性。还提供了使用这种化合物的方法和含有这种化合物的组合物来治疗间隙连接障碍。

  公开号：

  US20090143425A1

文献信息

• Compounds affecting gap junction activity
  申请人：Hua Duy H.

  公开号：US08809368B2

  公开（公告）日：2014-08-19

  This invention relates to novel quinoline compounds which affect gap junction activity. Also provided are methods of using such compounds and compositions containing the compounds to treat gap junction disorders.

  本发明涉及影响间隙连接活性的新奎奴啉化合物。还提供了使用这种化合物的方法和含有该化合物的组合物来治疗间隙连接障碍。
• COMPOUNDS AFFECTING GAP JUNCTION ACTIVITY
  申请人：HUA Duy H.

  公开号：US20090143425A1

  公开（公告）日：2009-06-04

  This invention relates to novel quinoline compounds which affect gap junction activity. Also provided are methods of using such compounds and compositions containing the compounds to treat gap junction disorders.

  本发明涉及新型喹啉化合物，其影响间隙连接活性。还提供了使用这种化合物的方法和含有这种化合物的组合物来治疗间隙连接障碍。
• Gap junction-enhancing agents for treatment of necrotizing enterocolitis and inflammatory bowel disease
  申请人：University of Pittsburgh—of the Commonwealth System of Higher Education

  公开号：US10172848B2

  公开（公告）日：2019-01-08

  The present invention relates to methods of reducing the risk of occurrence of, and/or treating, necrotizing enterocolitis (“NEC”) or inflammatory bowel disease (“IBD”) comprising administering, to a subject in need of such treatment, an effective amount of a gap junction enhancing agent (“GJEA”), for example a peptide (“GJP”) or peptide analog (“GJPA”). It is based, at least in part, on the discovery that greater functionality of gap junctions between enterocytes increases their rate of migration and reduces the severity of intestinal inflammation.

  本发明涉及降低坏死性小肠结肠炎（"NEC"）或炎症性肠病（"IBD"）发生风险和/或治疗坏死性小肠结肠炎（"NEC"）或炎症性肠病（"IBD"）的方法，包括向需要此类治疗的受试者施用有效量的间隙连接增强剂（"GJEA"），例如多肽（"GJP"）或多肽类似物（"GJPA"）。它至少部分是基于这样的发现：肠细胞之间的间隙连接功能增强，可提高肠细胞的迁移率，减轻肠道炎症的严重程度。
• WO2007/127930
  申请人：——

  公开号：——

  公开（公告）日：——
• GAP JUNCTION-ENHANCING AGENTS FOR TREATMENT OF NECROTIZING ENTEROCOLITIS AND INFLAMMATORY BOWEL DISEASE
  申请人：UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

  公开号：US20190070168A1

  公开（公告）日：2019-03-07

  The present invention relates to methods of reducing the risk of occurrence of, and/or treating, necrotizing enterocolitis (“NEC”) or inflammatory bowel disease (“IBD”) comprising administering, to a subject in need of such treatment, an effective amount of a gap junction enhancing agent (“GJEA”), for example a peptide (“GJP”) or peptide analog (“GJPA”). It is based, at least in part, on the discovery that greater functionality of gap junctions between enterocytes increases their rate of migration and reduces the severity of intestinal inflammation.