7-(1-Methylpyrazol-4-yl)-4-(propan-2-ylamino)quinoline-3-carbonitrile | 1428336-97-3

• 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: 7-(1-Methylpyrazol-4-yl)-4-(propan-2-ylamino)quinoline-3-carbonitrile
• 英文别名: 7-(1-methylpyrazol-4-yl)-4-(propan-2-ylamino)quinoline-3-carbonitrile
• CAS: 1428336-97-3
• 化学式: C₁₇H₁₇N₅
• 分子量: 291.355
• InChiKey: XXPMZJXWFXBNBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-碘苯胺 在 四(三苯基膦)钯 、 potassium carbonate 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 、 水 为溶剂， 生成 7-(1-Methylpyrazol-4-yl)-4-(propan-2-ylamino)quinoline-3-carbonitrile
  参考文献：
  名称：

  Discovery of 4-alkylamino-7-aryl-3-cyanoquinoline LRRK2 kinase inhibitors

  摘要：

  Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with familial Parkinson's disease (PD). The kinase activity of this complex protein is increased by pathogenic mutations. Inhibition of LRRK2 kinase activity has therefore emerged as a promising approach for the treatment of PD. Herein we report our findings on a series of 4-alkylamino-7-aryl-3-cyanoquinolines that exhibit kinase inhibitory activity against both wild type and G2019S mutant LRRK2. Activity was determined in both biochemical and cellular assays. Compound 14 was further evaluated in an in vivo pharmacodynamic study and found to significantly inhibit Ser935 phosphorylation after oral dosing. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.041

文献信息

• Discovery of 4-alkylamino-7-aryl-3-cyanoquinoline LRRK2 kinase inhibitors
  作者：Albert W. Garofalo、Marc Adler、Danielle L. Aubele、Elizabeth F. Brigham、David Chian、Maurizio Franzini、Erich Goldbach、Grace T. Kwong、Ruth Motter、Gary D. Probst、Kevin P. Quinn、Lany Ruslim、Hing L. Sham、Danny Tam、Pearl Tanaka、Anh P. Truong、Xiaocong M. Ye、Zhao Ren

  DOI：10.1016/j.bmcl.2013.02.041

  日期：2013.4

  Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with familial Parkinson's disease (PD). The kinase activity of this complex protein is increased by pathogenic mutations. Inhibition of LRRK2 kinase activity has therefore emerged as a promising approach for the treatment of PD. Herein we report our findings on a series of 4-alkylamino-7-aryl-3-cyanoquinolines that exhibit kinase inhibitory activity against both wild type and G2019S mutant LRRK2. Activity was determined in both biochemical and cellular assays. Compound 14 was further evaluated in an in vivo pharmacodynamic study and found to significantly inhibit Ser935 phosphorylation after oral dosing. (C) 2013 Elsevier Ltd. All rights reserved.