4-({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}-amino)-7-[(1E)-3-pyrrolidin-1-ylprop-1-enyl]quinoline-3-carbonitrile | 946490-32-0

• 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)-3-pyrrolidin-1-ylprop-1-enyl]quinoline-3-carbonitrile
• 英文别名: 4-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylanilino]-7-[(E)-3-pyrrolidin-1-ylprop-1-enyl]quinoline-3-carbonitrile
• CAS: 946490-32-0
• 化学式: C₂₇H₂₅ClN₆S
• 分子量: 501.055
• InChiKey: KJIKEFFIRMLEEQ-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 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：

  四氢吡咯 、 (2E)-3-[4-({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}amino)-3-cyanoquinolin-7-yl]prop-2-enyl acetate 生成 4-({3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}-amino)-7-[(1E)-3-pyrrolidin-1-ylprop-1-enyl]quinoline-3-carbonitrile
  参考文献：
  名称：

  PREPARATION OF 7-ALKENYL-3 QUINOLINECARBONITRILES VIA A PALLADIUM MEDIATED COUPLING REACTION

  摘要：

  本发明涉及一种制备式（I）化合物的过程：其中A、R1-R3、X、s、t、u、m和Z在此定义，包括在Pd（O）金属存在下将式（II）试剂与式（III）化合物或其盐反应的步骤。本发明的另一个方面是一种制备式（VI）化合物的方法。

  公开号：

  US20090099356A1

文献信息

• 4-Anilino-7-alkenylquinoline-3-carbonitriles as potent MEK1 kinase inhibitors
  作者：Dan M. Berger、Minu Dutia、Dennis Powell、Middleton B. Floyd、Nancy Torres、Robert Mallon、Donald Wojciechowicz、Steven Kim、Larry Feldberg、Karen Collins、Inder Chaudhary

  DOI：10.1016/j.bmc.2008.09.009

  日期：2008.10

  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.