7-(2-[(18)F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile | 1265536-52-4

• 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: 7-(2-[(18)F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile
• 英文别名: 7-(2-(18F)fluoranylethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile
• CAS: 1265536-52-4
• 化学式: C₁₀H₁₀FN₅
• 分子量: 218.223
• InChiKey: SSLYZBHFIPUSPF-KXMUYVCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-氯-5-甲基吡唑并[1,5-a]嘧啶-3-甲腈 在 4-二甲氨基吡啶 、 potassium [¹⁸F]fluoride 、 三乙胺 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 16.83h， 生成 7-(2-[(18)F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile
  参考文献：
  名称：

  Synthesis and biological evaluation of novel F-18 labeled pyrazolo[1,5-a]pyrimidine derivatives: Potential PET imaging agents for tumor detection

  摘要：

  Two novel pyrazolo[1,5-a]pyrimidine derivatives, 7-(2-[F-18]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([F-18]FEMPPC, [F-18]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[F-18]fluoro-4-nitrobenzamide ([F-18]FCMPPN, [F-18]2), have been designed and successively labeled with F-18 by the nucleophilic substitution employing tosylate and nitryl as leaving groups, respectively. The radiochemical synthesis of both compounds was completed within 60 min with final high-performance liquid chromatography purification included. The corresponding radiochemical yields (without decay correction) were approximately 35% and 30%, respectively. Meanwhile, we compared the uptake characteristics of [F-18]1 and [F-18]2 with those of [F-18]FDG and L-[F-18]FET in S180 tumor cells. Furthermore, the tumor uptake of [F-18]1 and [F-18]2 was assessed in mice bearing S180 tumor and compared with [F-18]FDG and L-[F-18]FET in the same animal model. In vitro cell uptake studies showed [F-18]1 had higher uptake than [F-18]FDG, [F-18]2 and L-[F-18]FET over the 2 h period. In ex vivo biodistribution showed tumor/brain uptake ratios of [F-18]2 were 12.35, 10.44, 8.69 and 5.13 at 15 min, 30 min, 60 min and 120 min post-injection, much higher than those of L-[F-18]FET (2.43, 2.54, 2.93 and 2.95) and [F-18]FDG (0.59, 0.61, 1.02 and 1.33) at the same time point. What's more, the uptake of [F-18]1 in tumor was 1.88, 4.37, 5.51, 2.95 and 2.88 at 5 min, 15 min, 30 min, 60 min and 120 min post-injection, respectively. There was a remarkable increasing trend before 30 min. The same trend was present for L-[F-18]FET before 30 min and [F-18]FDG before 60 min. Additionally, the tumor/brain uptake ratios of [F-18]1 were superior to those of [F-18]FDG at all the selected time points, the tumor/muscle and tumor/blood uptake ratios of [F-18]1 at 30 min were higher than those of L-[F-18]FET at the same time point. MicroPET image of [F-18]1 administered into S180 tumor-bearing mouse acquired at 30 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggest that compound [F-18]1 could be a new probe for PET tumor imaging. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.072

文献信息

• Synthesis and biological evaluation of novel F-18 labeled pyrazolo[1,5-a]pyrimidine derivatives: Potential PET imaging agents for tumor detection
  作者：Jingli Xu、Hang Liu、Guixia Li、Yong He、Rui Ding、Xiao Wang、Man Feng、Shuting Zhang、Yurong Chen、Shilei Li、Mingxia Zhao、Chuanmin Qi、Yonghong Dang

  DOI：10.1016/j.bmcl.2011.06.072

  日期：2011.8

  Two novel pyrazolo[1,5-a]pyrimidine derivatives, 7-(2-[F-18]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([F-18]FEMPPC, [F-18]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[F-18]fluoro-4-nitrobenzamide ([F-18]FCMPPN, [F-18]2), have been designed and successively labeled with F-18 by the nucleophilic substitution employing tosylate and nitryl as leaving groups, respectively. The radiochemical synthesis of both compounds was completed within 60 min with final high-performance liquid chromatography purification included. The corresponding radiochemical yields (without decay correction) were approximately 35% and 30%, respectively. Meanwhile, we compared the uptake characteristics of [F-18]1 and [F-18]2 with those of [F-18]FDG and L-[F-18]FET in S180 tumor cells. Furthermore, the tumor uptake of [F-18]1 and [F-18]2 was assessed in mice bearing S180 tumor and compared with [F-18]FDG and L-[F-18]FET in the same animal model. In vitro cell uptake studies showed [F-18]1 had higher uptake than [F-18]FDG, [F-18]2 and L-[F-18]FET over the 2 h period. In ex vivo biodistribution showed tumor/brain uptake ratios of [F-18]2 were 12.35, 10.44, 8.69 and 5.13 at 15 min, 30 min, 60 min and 120 min post-injection, much higher than those of L-[F-18]FET (2.43, 2.54, 2.93 and 2.95) and [F-18]FDG (0.59, 0.61, 1.02 and 1.33) at the same time point. What's more, the uptake of [F-18]1 in tumor was 1.88, 4.37, 5.51, 2.95 and 2.88 at 5 min, 15 min, 30 min, 60 min and 120 min post-injection, respectively. There was a remarkable increasing trend before 30 min. The same trend was present for L-[F-18]FET before 30 min and [F-18]FDG before 60 min. Additionally, the tumor/brain uptake ratios of [F-18]1 were superior to those of [F-18]FDG at all the selected time points, the tumor/muscle and tumor/blood uptake ratios of [F-18]1 at 30 min were higher than those of L-[F-18]FET at the same time point. MicroPET image of [F-18]1 administered into S180 tumor-bearing mouse acquired at 30 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggest that compound [F-18]1 could be a new probe for PET tumor imaging. (C) 2011 Elsevier Ltd. All rights reserved.