4-(3-Chloro-4-fluoro-phenylamino)-6-[(1H-pyrazol-3-ylmethyl)-amino]-quinoline-3-carbonitrile

• 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: 4-(3-Chloro-4-fluoro-phenylamino)-6-[(1H-pyrazol-3-ylmethyl)-amino]-quinoline-3-carbonitrile
• 英文别名: 4-[(3-chloro-4-fluorophenyl)amino]-6-[(1H-pyrazol-3-ylmethyl)amino]quinoline-3-carbonitrile；6-((1H-pyrazol-3-yl)methylamino)-4-(3-chloro-4-fluorophenylamino)quinoline-3-carbonitrile；4-(3-chloro-4-fluoroanilino)-6-(1H-pyrazol-5-ylmethylamino)quinoline-3-carbonitrile
• 化学式: C₂₀H₁₄ClFN₆
• 分子量: 392.823
• InChiKey: CMLPPPWSDQLMBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  89.4
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-quinoline-3-carbonitrile 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 4-(3-Chloro-4-fluoro-phenylamino)-6-[(1H-pyrazol-3-ylmethyl)-amino]-quinoline-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

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。
• 3-CYANOQUINOLINE INHIBITORS OF TPL2 KINASE AND METHODS OF MAKING AND USING THE SAME
  申请人：Wyeth

  公开号：EP1888529A2

  公开（公告）日：2008-02-20
• [EN] 3-CYANOQUINOLINE INHIBITORS OF TPL2 KINASE AND METHODS OF MAKING AND USING THE SAME<br/>[FR] INHIBITEURS 3-CYANOQUINOLINE DE LA TPL2 KINASE ET PROCEDES DE PRODUCTION ET D'UTILISATION ASSOCIES
  申请人：WYETH CORP

  公开号：WO2006124692A2

  公开（公告）日：2006-11-23

  [EN] The present invention provides compounds of formula (I): CHEMICAL FORMULA SHOULD BE INSERTED HERE AS IT APPEARS ON THE ABSTRACT IN PAPER FORM. (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, 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.
  [FR] L'invention concerne des composés de formule (I): (I), et des sels pharmaceutiquement acceptables de ces composés, R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, m et n étant comme définis dans la description. La présente invention porte également sur des procédés pour produire des composés de formule (I), et sur des méthodes pour traiter des maladies inflammatoires telles que la polyarthrite rhumatoïde chez un mammifère, par administration d'une quantité thérapeutiquement suffisante d'un composé de formule (I) au mammifère.
• Inhibition of Tpl2 kinase and TNFα production with quinoline-3-carbonitriles for the treatment of rheumatoid arthritis
  作者：Yonghan Hu、Neal Green、Lori K. Gavrin、Kristin Janz、Neelu Kaila、Huan-Qiu Li、Jennifer R. Thomason、John W. Cuozzo、J. Perry Hall、Sang Hsu、Cheryl Nickerson-Nutter、Jean-Baptiste Telliez、Lih-Ling Lin、Steve Tam

  DOI：10.1016/j.bmcl.2006.08.102

  日期：2006.12

  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.