2-([1,2,4]噻唑并[1,5-a]吡啶-6-基)-1-(5-氟-6-甲基吡啶-2-基)乙酮 | 1132610-47-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 中文名称: 2-([1,2,4]噻唑并[1,5-a]吡啶-6-基)-1-(5-氟-6-甲基吡啶-2-基)乙酮
• 中文别名: 1-(5-氟-6-甲基-2-吡啶基)-2-[1,2,4]三唑[1,5-a]吡啶基-6-基-乙酮；1-(5-氟-6-甲基-2-吡啶基)-2-[1,2,4]三唑[1,5-A]吡啶基-6-基-乙酮
• 英文名称: 2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(5-fluoro-6-methylpyridin-2-yl)ethanone
• 英文别名: 1-(5-fluoro-6-methylpyridin-2-yl)-2-[1,2,4]triazolo-[1,5-a]pyridin-6-yl-ethanone；2-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-1-(5-fluoro-6-methylpyridin-2-yl)ethanone；1-(5-fluoro-6-methylpyridin-2-yl)-2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)ethanone
• CAS: 1132610-47-9
• 化学式: C₁₄H₁₁FN₄O
• 分子量: 270.266
• InChiKey: JYFYKETYUYEBDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  60.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-([1,2,4]噻唑并[1,5-a]吡啶-6-基)-1-(5-氟-6-甲基吡啶-2-基)乙酮 在 氢溴酸 作用下， 以 水 、 二甲基亚砜 为溶剂， 以91%的产率得到1-(5-氟-6-甲基吡啶-2-基)-2-([1,2,4]三唑并[1,5-a]吡啶-6-基)乙烷-1,2-二酮
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-(fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles as inhibitors of transforming growth factor-β type I receptor kinase

  摘要：

  To further optimize a clinical candidate 5 (EW-7197), a series of 5-(3-, 4-, or 5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles 19a-l have been synthesized and evaluated for their TGF-beta type I receptor kinase (ALK5) and p38 alpha MAP kinase inhibitory activity in an enzyme assay. The 5-(5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4] triazolo[1,5-a] pyridin-6-yl)imidazoles 19h-1 displayed the similar level of potency to that of 5 against both ALK5 (IC50 = 7.68-13.70 nM) and p38 alpha MAP kinase (IC50 = 1240-3370 nM). Among them, 19j inhibited ALK5 with IC50 value of 7.68 nM in a kinase assay and displayed 82% inhibition at 100 nM in a luciferase reporter assay. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.058
• 作为产物：
  描述：

  3-fluoro-6-iodo-2-methylpyridine 在 异丙基氯化镁 、 caesium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 异丙醇 为溶剂， 反应 39.0h， 生成 2-([1,2,4]噻唑并[1,5-a]吡啶-6-基)-1-(5-氟-6-甲基吡啶-2-基)乙酮
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-(fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles as inhibitors of transforming growth factor-β type I receptor kinase

  摘要：

  To further optimize a clinical candidate 5 (EW-7197), a series of 5-(3-, 4-, or 5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles 19a-l have been synthesized and evaluated for their TGF-beta type I receptor kinase (ALK5) and p38 alpha MAP kinase inhibitory activity in an enzyme assay. The 5-(5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4] triazolo[1,5-a] pyridin-6-yl)imidazoles 19h-1 displayed the similar level of potency to that of 5 against both ALK5 (IC50 = 7.68-13.70 nM) and p38 alpha MAP kinase (IC50 = 1240-3370 nM). Among them, 19j inhibited ALK5 with IC50 value of 7.68 nM in a kinase assay and displayed 82% inhibition at 100 nM in a luciferase reporter assay. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.058

文献信息

• 2-Aminoimidazoles inhibitors of TGF-β receptor 1
  作者：Dominique Bonafoux、Claudio Chuaqui、P. Ann Boriack-Sjodin、Chris Fitch、Gretchen Hankins、Serene Josiah、Cheryl Black、Gregg Hetu、Leona Ling、Wen-Cherng Lee

  DOI：10.1016/j.bmcl.2008.11.119

  日期：2009.2

  The 4-(5-fluoro-6-methyl-pyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-ylamine 3 is a potent and selective inhibitor of TGF-betaR1. Substitution of the amino group of 3 typically led to a slight decrease in the affinity for the receptor and in TGF-beta-inducted PAI-luciferase reporter activity. However, 2-acetamidoimidazoles were identified as attractive candidates for further optimization as a result of their significant activity combined to their superior pharmacokinetic profile.
• Synthesis and biological evaluation of 5-(fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles as inhibitors of transforming growth factor-β type I receptor kinase
  作者：Maddeboina Krishnaiah、Cheng Hua Jin、Yhun Yhong Sheen、Dae-Kee Kim

  DOI：10.1016/j.bmcl.2015.09.058

  日期：2015.11

  To further optimize a clinical candidate 5 (EW-7197), a series of 5-(3-, 4-, or 5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles 19a-l have been synthesized and evaluated for their TGF-beta type I receptor kinase (ALK5) and p38 alpha MAP kinase inhibitory activity in an enzyme assay. The 5-(5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4] triazolo[1,5-a] pyridin-6-yl)imidazoles 19h-1 displayed the similar level of potency to that of 5 against both ALK5 (IC50 = 7.68-13.70 nM) and p38 alpha MAP kinase (IC50 = 1240-3370 nM). Among them, 19j inhibited ALK5 with IC50 value of 7.68 nM in a kinase assay and displayed 82% inhibition at 100 nM in a luciferase reporter assay. (C) 2015 Elsevier Ltd. All rights reserved.