6-溴-4-(3-氯-4-氟苯胺基)喹啉-3-甲腈 | 915369-04-9

• 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
• 中文名称: 6-溴-4-(3-氯-4-氟苯胺基)喹啉-3-甲腈
• 英文名称: 6-bromo-N-(3-chloro-4-fluoro-phenyl)-quinoline-3-carbnitrile-4-amine
• 英文别名: 6-bromo-4-((3-chloro-4-fluorophenyl)amino)quinoline-3-carbonitrile；6-bromo-4-(3-chloro-4-fluoro-phenylamino)-quinoline-3-carbonitrile；6-Bromo-4-(3-chloro-4-fluoroanilino)quinoline-3-carbonitrile
• CAS: 915369-04-9
• 化学式: C₁₆H₈BrClFN₃
• 分子量: 376.615
• InChiKey: IAAKBYQRKJXESB-UHFFFAOYSA-N

物化性质

• 沸点：
  487.5±45.0 °C(Predicted)
• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  48.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-溴-4-(3-氯-4-氟苯胺基)喹啉-3-甲腈 在 palladium on activated charcoal 四(三苯基膦)钯 、 氢气 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 145.0h， 生成 4-(3-Chloro-4-fluorophenylamino)-6-phenethylquinoline-3-carbonitrile
  参考文献：
  名称：

  Inhibition of Tpl2 kinase and TNFα production with quinoline-3-carbonitriles for the treatment of rheumatoid arthritis

  摘要：

  The synthesis and structure-activity studies of a series of quinoline-3-carbonitriles as inhibitors of Tpl2 kinase are described. Potent inhibitors of Tpl2 kinase with selectivity against a panel of selected kinases in enzymatic assays and specificity in cell-based phosphorylation assays in LPS-treated human monocytes were identified. Selected inhibitors with moderate activity in human whole blood assay effectively inhibited LPS/D-Gal induced TNFalpha release when administered intraperitoneally in mice.

  DOI：

  10.1016/j.bmcl.2006.08.102
• 作为产物：
  描述：

  ethyl (Z)-3-[(4-bromophenyl)amino]-2-cyanoprop-2-enoate 以 乙醇 为溶剂， 反应 12.0h， 生成 6-溴-4-(3-氯-4-氟苯胺基)喹啉-3-甲腈
  参考文献：
  名称：

  Inhibition of Tpl2 kinase and TNFα production with quinoline-3-carbonitriles for the treatment of rheumatoid arthritis

  摘要：

  The synthesis and structure-activity studies of a series of quinoline-3-carbonitriles as inhibitors of Tpl2 kinase are described. Potent inhibitors of Tpl2 kinase with selectivity against a panel of selected kinases in enzymatic assays and specificity in cell-based phosphorylation assays in LPS-treated human monocytes were identified. Selected inhibitors with moderate activity in human whole blood assay effectively inhibited LPS/D-Gal induced TNFalpha release when administered intraperitoneally in mice.

  DOI：

  10.1016/j.bmcl.2006.08.102

文献信息

• 3-Cyanoquinoline inhibitors of Tpl2 kinase and methods of making and using the same
  申请人：Green Jeffrey Neal

  公开号：US20060264460A1

  公开（公告）日：2006-11-23

  The present invention provides compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , m and n are defined as described herein. The invention also provides methods of making the compounds of formula (I), and methods of treating inflammatory diseases, such as rheumatoid arthritis, in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) to the mammal.

  本发明提供了如下式（I）的化合物及其药用可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8、m和n的定义如本文所述。该发明还提供了制备如式（I）化合物的方法，以及治疗炎症性疾病（如类风湿性关节炎）的方法，包括向哺乳动物施用如式（I）化合物的治疗有效量。
• [EN] COMBINATION WITH CHECKPOINT INHIBITORS TO TREAT CANCER<br/>[FR] COMBINAISON D'INHIBITEURS DE POINTS DE CONTRÔLE POUR LE TRAITEMENT DU CANCER
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2020215037A1

  公开（公告）日：2020-10-22

  A combination comprising a compound of Formula (I) and/or Formula (Ia), or a pharmaceutically acceptable salt thereof, and at least one immune checkpoint modulator. Methods for the prevention and treatment of a cancer comprises administering to a subject in need thereof, a therapeutically effective amount of a combination, the combination comprising: a compound of Formula (I) and/or Formula (Ia), or a pharmaceutically acceptable salt thereof, and at least one immune checkpoint modulator.

  一种组合物包括化合物的公式(I)和/或公式(Ia)，或其药用可接受的盐，以及至少一种免疫检查点调节剂。预防和治疗癌症的方法包括向需要的受试者施用该组合物的治疗有效量，该组合物包括：化合物的公式(I)和/或公式(Ia)，或其药用可接受的盐，以及至少一种免疫检查点调节剂。
• Small molecule inhibitors of EGFR and PI3K
  申请人：The Regents of the University of Michigan

  公开号：US10206924B2

  公开（公告）日：2019-02-19

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazoline structure or a quinoline structure which function as dual inhibitors of EGFR proteins and PI3K proteins, and their use as therapeutics for the treatment of cancer and other diseases.

  本发明属于药物化学领域。特别是，本发明涉及一类具有喹唑啉结构或喹啉结构的新型小分子，它们可作为表皮生长因子受体蛋白和 PI3K 蛋白的双重抑制剂，并可用作治疗癌症和其他疾病的疗法。
• [EN] SMALL MOLECULE INHIBITORS OF EGFR AND PI3K<br/>[FR] INHIBITEURS À PETITE MOLÉCULE DE L'EGFR ET DE PI3K
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2016100347A3

  公开（公告）日：2016-08-18
• Synthesis and photophysical properties of a fluorescent cyanoquinoline probe for profiling ERBB2 kinase inhibitor response
  作者：Heajin Lee、Ralf Landgraf、James N. Wilson

  DOI：10.1016/j.bmc.2017.09.034

  日期：2017.11

  A fluorescent probe targeting the ERBB2 receptor tyrosine was designed, synthesized and evaluated as reporter of ERBB2 dynamics in overexpressing BT474, i.e. Her2(+), cells. Two cyanoquinazoline (CQ) probes modeled after type-I (CQ1) or active state and type-II (CQ2) or inactive state inhibitors were designed and synthesized with extended p systems that impart binding-induced, turn-on fluorescence. Solution spectroscopy revealed that CQ1 exhibited attractive photophysical properties and displayed turn-on emission in the presence of purified, soluble ERBB2 kinase domain, while CQ2 was found to be non-emissive, likely due to quenching via a photoinduced electron transfer mechanism. Live cell imaging with CQ1 revealed that this probe targeted an intracellular population of ERBB2, which increased following treatment with type-I inhibitors, gefinitib and canertinib, but showed no response to type-II inhibitors. CQ1 thus provides a novel means of imaging the dynamic response of ERBB2(+) cells to kinase inhibitors. (C) 2017 Elsevier Ltd. All rights reserved.