N-(3-ethynylphenyl)-6-(2-[18F]fluoroethoxy)-7-methoxyquinazolin-4-amine | 1389355-29-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(3-ethynylphenyl)-6-(2-[18F]fluoroethoxy)-7-methoxyquinazolin-4-amine
• 英文别名: N-(3-ethynylphenyl)-6-(2-(18F)fluoranylethoxy)-7-methoxyquinazolin-4-amine
• CAS: 1389355-29-6
• 化学式: C₁₉H₁₆FN₃O₂
• 分子量: 336.355
• InChiKey: UFHWLNVXVMPORC-LRFGSCOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酸乙酯 在 吡啶 、 4-二甲氨基吡啶 、 甲烷磺酸 、 L-蛋氨酸 、 水 、 potassium hydroxide 、 sodium hydroxide 、 三氯氧磷 作用下， 以 甲醇 、 二甲基亚砜 、 异丙醇 、 甲苯 为溶剂， 反应 0.25h， 生成 N-(3-ethynylphenyl)-6-(2-[18F]fluoroethoxy)-7-methoxyquinazolin-4-amine
  参考文献：
  名称：

  Synthesis and evaluation of novel F-18 labeled 4-aminoquinazoline derivatives: Potential PET imaging agents for tumor detection

  摘要：

  Three novel F-18-labeled 4-aminoquinazoline derivatives, N-(3-chloro-4-fluorophenyl)-6-(2-[F-18] fluoroethoxy)-7-methoxyquinazolin-4-amine([F-18]1), N-(3-ethynylphenyl)-6-(2-[F-18] fluoroethoxy)-7-methoxyquinazolin-4-amine([F-18]2), and N-(3-bromophenyl)-6-(2-[(18F)]fluoroethoxy)-7-methoxyquinazolin- 4-amine([F-18]3) were synthesized and radiolabeled by two-step reaction with overall radiochemical yield of 21-24% (without decay corrected). Then we carried out their biodistribution experiments in S180 tumor-bearing mice. Results showed that they had certain concentration accumulation in tumor and fast clearance from muscle and blood. It was encouraging that [F-18]3 was competitive among three F-18-labeled 4-aminoquinazoline derivatives in some aspects such as tumor/muscle uptake ratio reaching 7.70 at 60 min post-injection, tumor/blood uptake ratio reaching 6.61 at 120 min post-injection. So we compared radioactivity characteristics of [F-18]3 with those of [F-18]-FDG and L-[F-18]-FET in the same animal model. The absolute radioactivity uptake of [F-18]3 in tumor reached 3.31 at 60 min p.i., which was slightly higher than [F-18]-FDG ( 2.16) and L-[F-18]-FET (2.75) at the same time phase. For [F-18]3, tumor/muscle uptake ratio peaked 7.70 at 60 min, which was obviously superior to those of [F-18]-FDG and L-[F-18]-FET at all time points. The tumor/brain uptake ratios of [F-18]3 were 10.36, 17.42, 41.11 at 30 min, 60 min and 120 min post-injection, respectively, and are much higher than those of L-[F-18] FET (2.54, 2.92 and 2.95) and [F-18]-FDG (0.61, 1.02 and 1.33) at the same time points. All these results indicate that [F-18]3 is promising to become a potential PET tumor imaging agent. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.069

文献信息

• Synthesis and evaluation of novel F-18 labeled 4-aminoquinazoline derivatives: Potential PET imaging agents for tumor detection
  作者：Yurong Chen、Man Feng、Shilei Li、Jingli Xu、Hongyu Ning、Yong He、Xiao Wang、Rui Ding、Chuanmin Qi

  DOI：10.1016/j.bmcl.2012.05.069

  日期：2012.7

  Three novel F-18-labeled 4-aminoquinazoline derivatives, N-(3-chloro-4-fluorophenyl)-6-(2-[F-18] fluoroethoxy)-7-methoxyquinazolin-4-amine([F-18]1), N-(3-ethynylphenyl)-6-(2-[F-18] fluoroethoxy)-7-methoxyquinazolin-4-amine([F-18]2), and N-(3-bromophenyl)-6-(2-[(18F)]fluoroethoxy)-7-methoxyquinazolin- 4-amine([F-18]3) were synthesized and radiolabeled by two-step reaction with overall radiochemical yield of 21-24% (without decay corrected). Then we carried out their biodistribution experiments in S180 tumor-bearing mice. Results showed that they had certain concentration accumulation in tumor and fast clearance from muscle and blood. It was encouraging that [F-18]3 was competitive among three F-18-labeled 4-aminoquinazoline derivatives in some aspects such as tumor/muscle uptake ratio reaching 7.70 at 60 min post-injection, tumor/blood uptake ratio reaching 6.61 at 120 min post-injection. So we compared radioactivity characteristics of [F-18]3 with those of [F-18]-FDG and L-[F-18]-FET in the same animal model. The absolute radioactivity uptake of [F-18]3 in tumor reached 3.31 at 60 min p.i., which was slightly higher than [F-18]-FDG ( 2.16) and L-[F-18]-FET (2.75) at the same time phase. For [F-18]3, tumor/muscle uptake ratio peaked 7.70 at 60 min, which was obviously superior to those of [F-18]-FDG and L-[F-18]-FET at all time points. The tumor/brain uptake ratios of [F-18]3 were 10.36, 17.42, 41.11 at 30 min, 60 min and 120 min post-injection, respectively, and are much higher than those of L-[F-18] FET (2.54, 2.92 and 2.95) and [F-18]-FDG (0.61, 1.02 and 1.33) at the same time points. All these results indicate that [F-18]3 is promising to become a potential PET tumor imaging agent. (C) 2012 Elsevier Ltd. All rights reserved.