2-(2-fluoroethyloxybenzyl)-4-(cis-3a,4,5,6,7,7a-hexahydroisoindolin-2-yl)-4-oxobutanoic acid | 1613033-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(2-fluoroethyloxybenzyl)-4-(cis-3a,4,5,6,7,7a-hexahydroisoindolin-2-yl)-4-oxobutanoic acid
• CAS: 1613033-27-4
• 化学式: C₂₁H₂₈FNO₄
• 分子量: 377.456
• InChiKey: FTVOZYHNCOUXGX-JWTNVVGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.32
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  66.84
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-(2-fluoroethyloxybenzyl)-4-(cis-3a,4,5,6,7,7a-hexahydroisoindolin-2-yl)-4-oxobutanoic acid 在 4-二甲氨基吡啶 、 三乙胺 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 9.0h， 生成 (2S)-2-(2-fluoroethyloxybenzyl)-4-(cis-3a,4,5,6,7,7a-hexahydroisoindolin-2-yl)-4-oxobutyl (R)-α-methoxy-α-(trifluoromethyl)phenylacetate
  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 、 palladium 10% on activated carbon 、 水 、 氢气 、 caesium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 60.0 ℃ 、101.33 kPa 条件下， 反应 33.0h， 生成 2-(2-fluoroethyloxybenzyl)-4-(cis-3a,4,5,6,7,7a-hexahydroisoindolin-2-yl)-4-oxobutanoic acid
  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