3-(2,4-dichlorophenyl)-2,5-dimethyl-N,N-dipropylpyrazolo[1,5-a]pyrimidin-7-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(2,4-dichlorophenyl)-2,5-dimethyl-N,N-dipropylpyrazolo[1,5-a]pyrimidin-7-amine
• 化学式: C₂₀H₂₄Cl₂N₄
• 分子量: 391.343
• InChiKey: JCRZUMWOIHFWLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  33.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-氨基-4-(2,4-二氯苯基)-3-甲基吡唑 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 26.5h， 生成 3-(2,4-dichlorophenyl)-2,5-dimethyl-N,N-dipropylpyrazolo[1,5-a]pyrimidin-7-amine
  参考文献：
  名称：

  Synthesis, F-18 radiolabeling, and microPET evaluation of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines as ligands of the corticotropin-releasing factor type-1 (CRF1) receptor

  摘要：

  A series of 3-(2,4-dichlorophenyl)-N-alkyl-N-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines were synthesized and evaluated as potential positron emission tomography (PET) tracers for the corticotropin-releasing factor type-1 (CRF1) receptor. Compounds 27, 28, 29, and 30 all displayed high binding affinity (<= 1.2 nM) to the CRF1 receptor when assessed by in vitro competition binding assays at 23 degrees C, whereas a decrease in affinity (>= 10-fold) was observed with compound 26. The logP(7.4) values of [F-18]26-[F-18] 29 were in the range of similar to 2.2-2.8 and microPET evaluation of [F-18]26-[F-18] 29 in an anesthetized male cynomolgus monkey demonstrated brain penetrance, but specific binding was not sufficient enough to differentiate regions of high CRF1 receptor density from regions of low CRF1 receptor density. Radioactivity uptake in the skull, and sphenoid bone and/or sphenoid sinus during studies with [F-18]28, [F-18]28-d(8), and [F-18]29 was attributed to a combination of [F-18]fluoride generated by metabolic defluorination of the radiotracer and binding of intact radiotracer to CRF1 receptors expressed on mast cells in the bone marrow. Uptake of [F-18]26 and [F-18]27 in the skull and sphenoid region was rapid but then steadily washed out which suggests that this behavior was the result of binding to CRF1 receptors expressed on mast cells in the bone marrow with no contribution from [F-18]fluoride. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.036