4-ethyl-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzoic acid | 1429618-03-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 4-ethyl-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzoic acid
• 英文别名: 4-Ethyl-3-(2-{pyrazolo[1,5-a]pyrimidin-6-yl}ethynyl)benzoic acid；4-ethyl-3-(2-pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzoic acid
• CAS: 1429618-03-0
• 化学式: C₁₇H₁₃N₃O₂
• 分子量: 291.309
• InChiKey: RPTLNQGKEBHGPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  67.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-ethyl-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzoic acid 在 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 tert-butyl [6-(4-{3-[4-ethyl-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzamido]-5-(trifluoromethyl)benzyl}piperazin-1-yl)-6-oxohexyl]carbamate
  参考文献：
  名称：

  10.1021/acs.jmedchem.4c00162

  摘要：

  DOI：

  10.1021/acs.jmedchem.4c00162
• 作为产物：
  描述：

  methyl 4-ethyl-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)-benzoate 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 以90%的产率得到4-ethyl-3-(pyrazolo[1,5-a]pyrimidin-6-ylethynyl)benzoic acid
  参考文献：
  名称：

  Discovery and Optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as Novel Selective and Orally Bioavailable Discoidin Domain Receptor 1 (DDR1) Inhibitors

  摘要：

  Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)-benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the enzymatic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, respectively, but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that 7rh bound with DDR1 with a K-d value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of 7rh were 0.035 and 0.008, respectively. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, respectively.

  DOI：

  10.1021/jm301824k