tert-butyl 4-(4-(8-cyclopentyl-5-methyl-7-oxo-6-trimethylstannyl-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)phenyl)piperazine-1-carboxylate | 1216994-56-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(4-(8-cyclopentyl-5-methyl-7-oxo-6-trimethylstannyl-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)phenyl)piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-[4-[(8-cyclopentyl-5-methyl-7-oxo-6-trimethylstannylpyrido[2,3-d]pyrimidin-2-yl)amino]phenyl]piperazine-1-carboxylate
• CAS: 1216994-56-7
• 化学式: C₃₁H₄₄N₆O₃Sn
• 分子量: 667.439
• InChiKey: AKVLIQWVOUJUDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.56
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-(8-cyclopentyl-5-methyl-7-oxo-6-trimethylstannyl-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)phenyl)piperazine-1-carboxylate 在 I⁽¹²⁴⁾INa 、 溶剂黄146 、 sodium hydroxide 、 三氟乙酸 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 0.5h， 生成 8-cyclopentyl-6-[(124)I]iodo-5-methyl-2-(4-(piperazin-1-yl)phenylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one
  参考文献：
  名称：

  Radiosynthesis and radiopharmacological evaluation of cyclin-dependent kinase 4 (Cdk4) inhibitors

  摘要：

  Tumor cells are characterized by their loss of growth control resulting from alterations in regulating pathways of the cell cycle, such as a deregulated cyclin-dependent kinase (Cdk) activity and/or Cdk expression. Appropriately radiolabeled Cdk4 inhibitors are discussed as promising molecular probes for imaging cell proliferation processes and tumor visualization by PET. This work describes the design, synthesis and radiopharmacological evaluation of two I-124-labeled Cdk4 inhibitors as potential radio-tracers for imaging of Cdk4 in vivo. Treatment of a solution containing labeling precursors with [I-124]NaI gave radiolabeled Cdk4 inhibitors [I-124]CKIA and [I-124]CKIB in radiochemical yields of up to 35%. I-124- labeled radiotracers [I-124]CKIA and [I-124]CKIB were used in cell uptake studies as well as biodistribution studies in Wistar rats and small-animal PET in tumor-bearing mice. In vitro radiotracer uptake studies in adherent tumor cells using [I-124]CKIA showed substantial uptake in HT-29 and FaDu cells (750-850% ID/mg protein [I-124]CKIA and 900-1000 %ID/mg protein [I-124]CKIB) after 1 h at 37 degrees C. Biodistribution of [I-124]CKIA and [I-124]CKIB showed rapid blood clearance of radioactivity and an accumulation as well as metabolization in the liver. Both radiotracers were administered intravenously to mouse FaDu xenograft tumor model and imaging studies were performed on a small-animal PET scanner. Both imaging techniques showed only little uptake of both radiotracers in the FaDu tumor xenografts. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.11.020