6-fluoro-2-(4-methoxyphenyl)quinoline-4-carboxylic acid | 436087-48-8

• 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-fluoro-2-(4-methoxyphenyl)quinoline-4-carboxylic acid
• CAS: 436087-48-8
• 化学式: C₁₇H₁₂FNO₃
• 分子量: 297.286
• InChiKey: JWCVGNKAPPYVKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-fluoro-2-(4-methoxyphenyl)quinoline-4-carboxylic acid 在 氯化亚砜 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 6-fluoro-N-(3-fluoro-4-(6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinolin-4-yloxy)phenyl)-2-(4-methoxyphenyl)quinoline-4-carboxamide
  参考文献：
  名称：

  Design, synthesis and antitumour activity of bisquinoline derivatives connected by 4-oxy-3-fluoroaniline moiety

  摘要：

  A series of novel bisquinoline derivatives connected by a 4-oxy-3-fluoroaniline moiety were synthesized and evaluated for their in vitro antitumour activities against a panel of five cancer cell lines (H460, HT-29, MKN-45, U87MG, and SMMC-7721). Most of compounds tested showed a potent activity and high selectivity towards the H460 and MKN-45 cell lines. Among the compounds tested, six (15d, 15e, 15m, 15n, 16a, and 16i) were further examined for their c-Met kinase activity; the compounds showed high efficacy with IC50 values in the single-digit nM range. An analysis of structure activity relationships indicated that an unsubstituted or a halogen-substituted phenyl ring on the 2-arylquinoline-4-carboxamide moiety was favourable for antitumour activity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.001
• 作为产物：
  描述：

  4-fluoroisonitrosoacetanilide 在 硫酸 、 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 6-fluoro-2-(4-methoxyphenyl)quinoline-4-carboxylic acid
  参考文献：
  名称：

  Design, synthesis and antitumour activity of bisquinoline derivatives connected by 4-oxy-3-fluoroaniline moiety

  摘要：

  A series of novel bisquinoline derivatives connected by a 4-oxy-3-fluoroaniline moiety were synthesized and evaluated for their in vitro antitumour activities against a panel of five cancer cell lines (H460, HT-29, MKN-45, U87MG, and SMMC-7721). Most of compounds tested showed a potent activity and high selectivity towards the H460 and MKN-45 cell lines. Among the compounds tested, six (15d, 15e, 15m, 15n, 16a, and 16i) were further examined for their c-Met kinase activity; the compounds showed high efficacy with IC50 values in the single-digit nM range. An analysis of structure activity relationships indicated that an unsubstituted or a halogen-substituted phenyl ring on the 2-arylquinoline-4-carboxamide moiety was favourable for antitumour activity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.001

文献信息

• Quinoline-4-methyl esters as human nonpancreatic secretory phospholipase A2 inhibitors
  作者：Yiran Wu、Zheng Chen、Ying Liu、Lanlan Yu、Lu Zhou、Suijia Yang、Luhua Lai

  DOI：10.1016/j.bmc.2011.04.039

  日期：2011.6

  A series of novel fused heterocycle methyl esters were designed and synthesized as human nonpancreatic secretory phospholipase A2 (hnps-PLA2) competitive inhibitors. Among the 22 synthesized compounds, 17 quinoline-4-methyl esters displayed hnps-PLA2 inhibition activity in the in vitro bioassay. The IC50 value for the best compound 3o was 1.5 μM. The structure-inhibition–activity relationships of the

  设计并合成了一系列新颖的稠合杂环甲基酯作为人非胰腺分泌型磷脂酶A 2（hnps-PLA 2）竞争性抑制剂。在22种合成化合物中，有17种喹啉-4-甲酯在体外生物测定中显示出hnps-PLA 2抑制活性。最佳化合物3o的IC 50值为1.5μM。使用分子对接研究了化合物的结构-抑制-活性关系。
• [EN] NOVEL PHENYL-QUINOLINE-CARBOXYLIC ACID PYRIDINE DERIVATIVES USEFUL AS MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS<br/>[FR] NOUVEAUX DÉRIVÉS DE PHÉNYLQUINOLÉINE-ACIDE CARBOXYLIQUE-PYRIDINE UTILES COMME MODULATEURS DES RÉCEPTEURS NICOTINIQUES À L'ACÉTYLCHOLINE
  申请人：NEUROSEARCH AS

  公开号：WO2010020672A1

  公开（公告）日：2010-02-25

  This invention relates to novel phenyl-quinoline-carboxylic acid pyridine derivatives, which are found to be modulators of the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

  本发明涉及新型苯基-喹啉-羧酸吡啶衍生物，发现它们是乙酰胆碱受体的调节剂。由于它们的药理特性，本发明的化合物可能对治疗与中枢神经系统（CNS）和外周神经系统（PNS）的胆碱能系统有关的疾病或障碍，平滑肌收缩有关的疾病或障碍，内分泌疾病或障碍，神经退行性疾病或障碍，炎症、疼痛以及由于化学物质滥用终止引起的戒断症状可能有用。
• SAR-Based Optimization of a 4-Quinoline Carboxylic Acid Analogue with Potent Antiviral Activity
  作者：Priyabrata Das、Xiaoyi Deng、Liang Zhang、Michael G. Roth、Beatriz M. A. Fontoura、Margaret A. Phillips、Jef K. De Brabander

  DOI：10.1021/ml300464h

  日期：2013.6.13

  It is established that drugs targeting viral proteins are at risk of generating resistant strains. However, drugs targeting host factors can potentially avoid this problem. Herein, we report structure-ctivity relationship studies leading to the discovery of a very potent lead compound 6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl) quinoline -4-carboxylic acid (C44) that inhibits human dihydroorotate dehydrogenase (DHODH) with an IC50 of 1 nM and viral replication of VSV and WSN-Influenza with an EC50 of 2 nM and 41 nM. We also solved the X-ray structure of human DHODH bound to C44, providing structural insight into the potent inhibition of biaryl ether analogues of brequinar.
• Design, synthesis and antitumour activity of bisquinoline derivatives connected by 4-oxy-3-fluoroaniline moiety
  作者：Sai Li、Qiang Huang、Yajing Liu、Xiaolong Zhang、Shuang Liu、Chao He、Ping Gong

  DOI：10.1016/j.ejmech.2013.04.001

  日期：2013.6

  A series of novel bisquinoline derivatives connected by a 4-oxy-3-fluoroaniline moiety were synthesized and evaluated for their in vitro antitumour activities against a panel of five cancer cell lines (H460, HT-29, MKN-45, U87MG, and SMMC-7721). Most of compounds tested showed a potent activity and high selectivity towards the H460 and MKN-45 cell lines. Among the compounds tested, six (15d, 15e, 15m, 15n, 16a, and 16i) were further examined for their c-Met kinase activity; the compounds showed high efficacy with IC50 values in the single-digit nM range. An analysis of structure activity relationships indicated that an unsubstituted or a halogen-substituted phenyl ring on the 2-arylquinoline-4-carboxamide moiety was favourable for antitumour activity. (C) 2013 Elsevier Masson SAS. All rights reserved.