3-[7-(2-methylphenyl)-4-oxo-3H-[1]benzothiolo[2,3-d]pyrimidin-2-yl]propanoic acid | 1297474-19-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 3-[7-(2-methylphenyl)-4-oxo-3H-[1]benzothiolo[2,3-d]pyrimidin-2-yl]propanoic acid
• CAS: 1297474-19-1
• 化学式: C₂₀H₁₆N₂O₃S
• 分子量: 364.425
• InChiKey: NGOFUPFTYDRPAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(o-tolyl)cyclohexanone 在 哌啶 、 盐酸 、 水 、 四氯苯醌 、 sulfur 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 正丁醇 为溶剂， 反应 19.0h， 生成 3-[7-(2-methylphenyl)-4-oxo-3H-[1]benzothiolo[2,3-d]pyrimidin-2-yl]propanoic acid
  参考文献：
  名称：

  Aryl extensions of thienopyrimidinones as fibroblast growth factor receptor 1 kinase inhibitors

  摘要：

  Optimization of thienopyrimidinone derivatives as FGFR1 kinase inhibitors is being pursued. The present results confirm predictions of computational modeling that an aryl substituent can be introduced at the 2-position in structure 3. The substituent is anticipated to project deeper into the binding site and provide opportunities for enhanced activity and selectivity. The most potent analog reported herein, 13, has a 4-hydroxyphenyl substituent and yields an IC(50) of 6 mu M for inhibition of phosphorylation by FGFR1 kinase. It was also found that the western anisole-containing substituent in 3 can be replaced by a propionic acid group with no loss in potency and with potentially significant gains in pharmacologically relevant properties. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2010.12.081

文献信息

• Aryl extensions of thienopyrimidinones as fibroblast growth factor receptor 1 kinase inhibitors
  作者：Anil R. Ekkati、Valsan Mandiyan、Krishna P. Ravindranathan、Jae H. Bae、Joseph Schlessinger、William L. Jorgensen

  DOI：10.1016/j.tetlet.2010.12.081

  日期：2011.4

  Optimization of thienopyrimidinone derivatives as FGFR1 kinase inhibitors is being pursued. The present results confirm predictions of computational modeling that an aryl substituent can be introduced at the 2-position in structure 3. The substituent is anticipated to project deeper into the binding site and provide opportunities for enhanced activity and selectivity. The most potent analog reported herein, 13, has a 4-hydroxyphenyl substituent and yields an IC(50) of 6 mu M for inhibition of phosphorylation by FGFR1 kinase. It was also found that the western anisole-containing substituent in 3 can be replaced by a propionic acid group with no loss in potency and with potentially significant gains in pharmacologically relevant properties. (C) 2010 Elsevier Ltd. All rights reserved.