3-(5-iodo-1H-indol-3-yl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole-2,5-dione | 1215293-98-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3-(5-iodo-1H-indol-3-yl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole-2,5-dione
• 英文别名: 3-(5-iodo-1H-indol-3-yl)-4-(3,4,5-trimethoxyphenyl)pyrrole-2,5-dione
• CAS: 1215293-98-3
• 化学式: C₂₁H₁₇IN₂O₅
• 分子量: 504.281
• InChiKey: KRICMVKKVCDVBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 2-(5-iodo-1H-indol-3-yl)-2-oxoacetate 、 2-(3,4,5-三甲氧基苯基)乙酰胺 在 potassium tert-butylate 、 水 、 氯化铵 作用下， 以 四氢呋喃 为溶剂， 以66%的产率得到3-(5-iodo-1H-indol-3-yl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Labeled 3-aryl-4-indolylmaleimide derivatives and their potential as angiogenic PET biomarkers

  摘要：

  In a continued effort to find a suitable PET tracer for visualization of angiogenic processes, we explored the 3,4-diarylmaleimide family, known to have high affinity and selectivity towards the VEGFR-TKs. One previously reported agent and three new halogen-containing 3,4-diarylmaleimide derivatives were synthesized. The four maleimide derivatives were evaluated for their affinity and selectivity towards the VEGFRs and exhibited promising results. An automated carbon-11 radiolabeling route with a total synthesis time of 50 min successfully labeled the lead compound, resulting in 1.55 +/- 0.15 GBq of tracer with a radiochemical yield of 20 +/- 2%, 96% radiochemical purity and a SA of 111 +/- 22 GBq/mu mol (EOB, n = 5). The tracer possessed high stability in in vitro blood stability tests and specific VEGFR-TK binding profiles in intact cell binding experiments. Tracer lipophilicity was evaluated in an n-octanol/phosphate buffer system giving a Log D-7.4 of 1.99 +/- 0.04. For the in vivo experiments, two animal models were used. The first was a U87 glioma tumor model, frequently reported in the literature and the second, a newly developed 293/KDR tumor model. Both models were validated for VEGFR-2 expression and used in in vivo biodistribution studies. These studies revealed low accumulation and rapid washout of the tracer from tumor tissue. High accumulation of activity in the liver prompted us to examine the tracer's in vitro stability to liver microsomes, revealing low resistance to P450 metabolism. In spite of encouraging in vitro results, the labeled lead tracer failed to accumulate in VEGFR-2 overexpressing tumors. It is possible that poor resistance to P450 metabolism reduces tracer's circulation leading to low tumor accumulation. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.12.004