4-({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}-amino)-7-[(1E)-4-piperidin-1-ylbut-1-enyl]quinoline-3-carbonitrile | 946490-31-9

• 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
• 英文名称: 4-({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}-amino)-7-[(1E)-4-piperidin-1-ylbut-1-enyl]quinoline-3-carbonitrile
• 英文别名: 4-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylanilino]-7-[(E)-4-piperidin-1-ylbut-1-enyl]quinoline-3-carbonitrile
• CAS: 946490-31-9
• 化学式: C₂₉H₂₉ClN₆S
• 分子量: 529.108
• InChiKey: XBJBBROJSDKTIY-XVNBXDOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  95.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  哌啶 、 (2E)-3-[4-({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}amino)-3-cyanoquinolin-7-yl]but-3-enyl 4-methylphenylsulfonate 以 四氢呋喃 为溶剂， 反应 20.0h， 以48%的产率得到4-({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}-amino)-7-[(1E)-4-piperidin-1-ylbut-1-enyl]quinoline-3-carbonitrile
  参考文献：
  名称：

  4-Anilino-7-alkenylquinoline-3-carbonitriles as potent MEK1 kinase inhibitors

  摘要：

  A series of substituted 7-alkenyl 4[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-3-quinolinecarbonitrile analogs were synthesized and evaluated as MEK1 kinase inhibitors. The synthetic details, structure-activity relationships, biological activity, and selected oral exposure studies of these analogs are described. From these studies, compound 5m was chosen as a strong candidate for further evaluation. The selectivity of 5m was ascertained against a panel of 17 kinases, where activity was observed against EGFR, Src, Lyn, and IR kinases. Western blot studies in WM-266 cells demonstrated that 5m inhibited phosphorylation of ERK, while additional kinase pathways tested showed no inhibition at up to 10 mu M of 5m. PK studies, as well as a xenograft and in vivo biomarker studies are described for 5m. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.009

文献信息

• PREPARATION OF 7-ALKENYL-3 QUINOLINECARBONITRILES VIA A PALLADIUM MEDIATED COUPLING REACTION
  申请人：Wang Yanong Daniel

  公开号：US20090099356A1

  公开（公告）日：2009-04-16

  The present invention is directed to a process for preparing compounds of formula (I): wherein A, R 1 -R 3 , X, s, t, u, m and Z are defined herein, comprising the step of reacting a reagent of formula (II): in the presence of Pd(O) metal with a compound of formula (III): or salts thereof. Another aspect of this invention is a method of preparing compounds of formula (VI).

  本发明涉及一种制备化合物的方法，其化学式如下（I）：其中A、R1-R3、X、s、t、u、m和Z在此处定义，包括以下步骤：在Pd（O）金属存在下，将化学式（II）的试剂与化学式（III）的化合物或其盐反应。本发明的另一个方面是制备化合物的方法，其化学式为（VI）。