2-(4-fluoroethyloxybenzyl)-4-(cis-3a,4,5,6,7,7a-hexahydroisoindolin-2-yl)-4-oxobutanoic acid | 1245944-84-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-(4-fluoroethyloxybenzyl)-4-(cis-3a,4,5,6,7,7a-hexahydroisoindolin-2-yl)-4-oxobutanoic acid
• 英文别名: 4-[(3aS,7aR)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-2-[[4-(2-fluoroethoxy)phenyl]methyl]-4-oxobutanoic acid
• CAS: 1245944-84-6
• 化学式: C₂₁H₂₈FNO₄
• 分子量: 377.456
• InChiKey: CTBSNEFZOGMTAX-JWTNVVGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-fluoroethyloxybenzyl)-4-(cis-3a,4,5,6,7,7a-hexahydroisoindolin-2-yl)-4-oxobutanoic acid 、 (S)-N-benzylmandelamide 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 生成 (S)-2-(benzylamino)-2-oxo-1-phenylethyl (S)-2-(4-(2-fluoroethoxy)benzyl)-4-((3aR,7aS)-octahydro-2H-isoindol-2-yl)-4-oxobutanoate
  参考文献：
  名称：

  EP2407455

  摘要：

  公开号：
• 作为产物：
  描述：

  methyl 2-(4-benzyloxybenzylidene)-4-oxo-4-(cis-3a,4,7,7a-tetrahydroisoindolin-2-yl)butanoate 在 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， 50.0~60.0 ℃ 、101.33 kPa 条件下， 反应 21.0h， 生成 2-(4-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

文献信息

• MOLECULAR PROBE PRECURSOR FOR PANCREATIC ISLET IMAGING AND USE OF SAME
  申请人：Kyoto University

  公开号：EP2407455A1

  公开（公告）日：2012-01-18

  A precursor of a molecular probe for imaging of pancreatic islets is a compound expressed as the following formula (I): wherein -V-X represents a substituent on a benzene ring, V represents a bond, R1, or OR1, R1 represents a C1-C6 alkylene group, R2 represents H (hydrogen atom), a C1-C6 alkyl group, a C7-C10 aralkyl group, or a protecting group, X represents a OMs group, a OTs group, a OTf group, Br (bromine atom), or I (iodine atom), and carbon marked with * is an asymmetric carbon atom.

  用于胰岛成像的分子探针的前体是下式 (I) 所表示的化合物： 其中 -V-X 代表苯环上的取代基，V 代表键、R1 或 OR1，R1 代表 C1-C6 亚烷基，R2 代表 H（氢原子）、C1-C6 烷基、C7-C10 芳烷基或保护基，X 代表 OMs 基、OTs 基、OTf 基、Br（溴原子）或 I（碘原子），标有 * 的碳是不对称碳原子。
• Precursor of Molecular Probe for Pancreatic Islet Imaging and Use of the Same
  申请人：Inagaki Nobuya

  公开号：US20120107239A1

  公开（公告）日：2012-05-03

  A precursor of a molecular probe for imaging of pancreatic islets is a compound expressed as the following formula (I): wherein -V-X represents a substituent on a benzene ring, V represents a bond, R 1 , of OR 1 , R 1 represents a C 1 -C 6 alkylene group, R 2 represents H (hydrogen atom), a C 1 -C 6 alkyl group, a C 7 -C 10 aralkyl group, or a protecting group, X represents a OMs group, a OTs group, a OTf group, Br (bromine atom), or I (iodine atom), and carbon marked with * is an asymmetric carbon atom.
• Synthesis and evaluation of 18F-labeled mitiglinide derivatives as positron emission tomography tracers for β-cell imaging
  作者：Hiroyuki Kimura、Hirokazu Matsuda、Hiroyuki Fujimoto、Kenji Arimitsu、Kentaro Toyoda、Eri Mukai、Hiroshi Nakamura、Yu Ogawa、Mikako Takagi、Masahiro Ono、Nobuya Inagaki、Hideo Saji

  DOI：10.1016/j.bmc.2014.04.059

  日期：2014.7

  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.
• EP2407455
  申请人：——

  公开号：——

  公开（公告）日：——