methyl 2-(2-benzyloxybenzylidene)-4-oxo-4-(cis-3a,4,7,7a-tetrahydroisoindolin-2-yl)butanoate | 1613033-21-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: methyl 2-(2-benzyloxybenzylidene)-4-oxo-4-(cis-3a,4,7,7a-tetrahydroisoindolin-2-yl)butanoate
• CAS: 1613033-21-8
• 化学式: C₂₇H₂₉NO₄
• 分子量: 431.532
• InChiKey: BZAOZXGBOBEQJV-ZRZAMGCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.64
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.84
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 2-(2-benzyloxybenzylidene)-4-oxo-4-(cis-3a,4,7,7a-tetrahydroisoindolin-2-yl)butanoate 在 potassium [¹⁸F]fluoride 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 caesium carbonate 、 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 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 40.0~140.0 ℃ 、101.33 kPa 条件下， 反应 0.17h， 生成
  参考文献：
  名称：

  Synthesis and evaluation of 18F-labeled mitiglinide derivatives as positron emission tomography tracers for β-cell imaging

  摘要：

  Measuring changes in beta-cell mass in vivo during progression of diabetes mellitus is important for understanding the pathogenesis, facilitating early diagnosis, and developing novel therapeutics for this disease. However, a non-invasive method has not been developed. A novel series of mitiglinide derivatives (o-FMIT, m-FMIT and p-FMIT; FMITs) were synthesized and their binding affinity for the sulfonylurea receptor 1 (SUR1) of pancreatic islets were evaluated by inhibition studies. (+)-(S)-o-FMIT had the highest affinity of our synthesized FMITs (IC50 = 1.8 mu M). (+)-(S)-o-[F-18]FMIT was obtained with radiochemical yield of 18% by radiofluorination of racemic precursor 7, hydrolysis, and optical resolution with chiral HPLC; its radiochemical purity was >99%. In biodistribution experiments using normal mice, (+)-(S)-o-[F-18]FMIT showed 1.94 +/- 0.42% ID/g of pancreatic uptake at 5 min p.i., and decreases in radioactivity in the liver (located close to the pancreas) was relatively rapid. Ex vivo autoradiography experiments using pancreatic sections confirmed accumulation of (+)-(S)-o-[F-18]FMIT in pancreatic beta-cells. These results suggest that (+)-(S)-o-[F-18]FMIT meets the basic requirements for an radiotracer, and could be a candidate positron emission tomography tracer for in vivo imaging of pancreatic beta-cells. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.059
• 作为产物：
  描述：

  在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 20.5h， 生成 methyl 2-(2-benzyloxybenzylidene)-4-oxo-4-(cis-3a,4,7,7a-tetrahydroisoindolin-2-yl)butanoate
  参考文献：
  名称：

  Synthesis and evaluation of 18F-labeled mitiglinide derivatives as positron emission tomography tracers for β-cell imaging

  摘要：

  Measuring changes in beta-cell mass in vivo during progression of diabetes mellitus is important for understanding the pathogenesis, facilitating early diagnosis, and developing novel therapeutics for this disease. However, a non-invasive method has not been developed. A novel series of mitiglinide derivatives (o-FMIT, m-FMIT and p-FMIT; FMITs) were synthesized and their binding affinity for the sulfonylurea receptor 1 (SUR1) of pancreatic islets were evaluated by inhibition studies. (+)-(S)-o-FMIT had the highest affinity of our synthesized FMITs (IC50 = 1.8 mu M). (+)-(S)-o-[F-18]FMIT was obtained with radiochemical yield of 18% by radiofluorination of racemic precursor 7, hydrolysis, and optical resolution with chiral HPLC; its radiochemical purity was >99%. In biodistribution experiments using normal mice, (+)-(S)-o-[F-18]FMIT showed 1.94 +/- 0.42% ID/g of pancreatic uptake at 5 min p.i., and decreases in radioactivity in the liver (located close to the pancreas) was relatively rapid. Ex vivo autoradiography experiments using pancreatic sections confirmed accumulation of (+)-(S)-o-[F-18]FMIT in pancreatic beta-cells. These results suggest that (+)-(S)-o-[F-18]FMIT meets the basic requirements for an radiotracer, and could be a candidate positron emission tomography tracer for in vivo imaging of pancreatic beta-cells. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.059