(R)-3-(2-(2-fluoroethoxy)benzyl)-4-hydroxy-1-((3aR,7aS)-octahydro-2H-isoindol-2-yl)butan-1-one | 1622934-72-8

• 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: (R)-3-(2-(2-fluoroethoxy)benzyl)-4-hydroxy-1-((3aR,7aS)-octahydro-2H-isoindol-2-yl)butan-1-one
• CAS: 1622934-72-8
• 化学式: C₂₁H₃₀FNO₃
• 分子量: 363.473
• InChiKey: ZRJGMXALZBKYSZ-QRQLOZEOSA-N

物化性质

• 沸点：
  554.7±50.0 °C(predicted)
• 密度：
  1.146±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.22
• 重原子数：
  26.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  49.77
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (R)-3-(2-(2-fluoroethoxy)benzyl)-4-hydroxy-1-((3aR,7aS)-octahydro-2H-isoindol-2-yl)butan-1-one 、 甲氧基-三氟甲基苯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 反应 5.0h， 以75%的产率得到(2R)-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：

  2-苄氧基苯甲醛 在 氯化亚砜 、 palladium 10% on activated carbon 、 水 、 氢气 、 乙酸酐 、 caesium carbonate 、 三乙胺 、 三氟乙酸 、 potassium hydroxide 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -10.0~120.0 ℃ 、101.33 kPa 条件下， 反应 63.5h， 生成 (R)-3-(2-(2-fluoroethoxy)benzyl)-4-hydroxy-1-((3aR,7aS)-octahydro-2H-isoindol-2-yl)butan-1-one
  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