2-(4-(dimethylamino)phenyl)benzo[d]oxazol-5-ol | 1383563-18-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-(dimethylamino)phenyl)benzo[d]oxazol-5-ol
• 英文别名: 2-[4-(Dimethylamino)phenyl]-1,3-benzoxazol-5-ol；2-[4-(dimethylamino)phenyl]-1,3-benzoxazol-5-ol
• CAS: 1383563-18-5
• 化学式: C₁₅H₁₄N₂O₂
• 分子量: 254.288
• InChiKey: BWOJSVZRONTERQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  49.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-(dimethylamino)phenyl)benzo[d]oxazol-5-ol 在 四丁基氟化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 4-(5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline
  参考文献：
  名称：

  Novel ¹⁸F-Labeled Benzoxazole Derivatives as Potential Positron Emission Tomography Probes for Imaging of Cerebral β-Amyloid Plaques in Alzheimer’s Disease

  摘要：

  Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[F-18]fluoroethoxy)ethoxy)ethoxy)benzo-[d]oxazol-2-yl)-N-methylaniline ([F-18]24) and 4-(5-(2-(2-[F-18]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline ([F-18]32), were synthesized and evaluated as probes for imaging cerebral beta-amyloid (A beta) plaques in living brain tissue by PET. [F-18]24 and [F-18]32 displayed high affinity for A beta(1-42) aggregates (K-1 = 9.3 and 3.9 nM, respectively). In vitro autoradiography with sections of post-mortem AD brain and transgenic mouse brain confirmed the affinity of these tracers. Initial high uptake into and rapid washout from the brain in normal mice were observed. [F-18]24 also displayed excellent binding to A beta plaques in ex vivo autoradiographic experiments with Tg2576 mice. Furthermore, small-animal PET studies demonstrated significant differences in the clearance profile after the administration of [F-18]24 between Tg2576 and wild-type mice. The results suggest [F-18]24 to be a useful PET agent for detecting A beta plaques in the living human brain.

  DOI：

  10.1021/jm300251n
• 作为产物：
  描述：

  4-甲氧基-2-硝基酚 在 palladium 10% on activated carbon 、 氢气 、 三溴化硼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 37.5h， 生成 2-(4-(dimethylamino)phenyl)benzo[d]oxazol-5-ol
  参考文献：
  名称：

  Novel ¹⁸F-Labeled Benzoxazole Derivatives as Potential Positron Emission Tomography Probes for Imaging of Cerebral β-Amyloid Plaques in Alzheimer’s Disease

  摘要：

  Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[F-18]fluoroethoxy)ethoxy)ethoxy)benzo-[d]oxazol-2-yl)-N-methylaniline ([F-18]24) and 4-(5-(2-(2-[F-18]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline ([F-18]32), were synthesized and evaluated as probes for imaging cerebral beta-amyloid (A beta) plaques in living brain tissue by PET. [F-18]24 and [F-18]32 displayed high affinity for A beta(1-42) aggregates (K-1 = 9.3 and 3.9 nM, respectively). In vitro autoradiography with sections of post-mortem AD brain and transgenic mouse brain confirmed the affinity of these tracers. Initial high uptake into and rapid washout from the brain in normal mice were observed. [F-18]24 also displayed excellent binding to A beta plaques in ex vivo autoradiographic experiments with Tg2576 mice. Furthermore, small-animal PET studies demonstrated significant differences in the clearance profile after the administration of [F-18]24 between Tg2576 and wild-type mice. The results suggest [F-18]24 to be a useful PET agent for detecting A beta plaques in the living human brain.

  DOI：

  10.1021/jm300251n

文献信息

• Synthesis and Monkey-PET Study of (<i>R</i>)- and (<i>S</i>)-¹⁸F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive <i>in Vivo</i> Kinetics
  作者：Yanping Yang、Xuedan Wang、Hui Yang、Hualong Fu、Jinming Zhang、Xiaojun Zhang、Jiapei Dai、Zhiyong Zhang、Chunping Lin、Yuzhi Guo、Mengchao Cui

  DOI：10.1021/acs.molpharmaceut.6b00643

  日期：2016.11.7

  This study describes an effective strategy to improve pharmacokinetics of A beta imaging agents, offering a novel class of (R)- and (S)-F-18-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward A beta aggregates with K-i values ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[F-18]28 possessed high binding potency (K-i = 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain(2min)/brain(60min) = 27.8) that is superior to well-established [F-18]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[F-18]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[F-18]28 clearly labeled A beta plaques both in vitro and ex vivo. These results might qualify (S)-[F-18]28 to detect A beta plaques with high signal-to-noise ratio.
• Synthesis and biological evaluation of novel technetium-99m labeled phenylbenzoxazole derivatives as potential imaging probes for β-amyloid plaques in brain
  作者：Xuedan Wang、Mengchao Cui、Pingrong Yu、Zijing Li、Yanping Yang、Hongmei Jia、Boli Liu

  DOI：10.1016/j.bmcl.2012.05.010

  日期：2012.7

  Two uncharged Tc-99m-labeled phenylbenzoxazole derivatives were biologically evaluated as potential imaging probes for beta-amyloid plaques. The Tc-99m and corresponding rhenium complexes were synthesized by coupling monoamine-monoamide dithiol (MAMA) and bis(aminoethanethiol) (BAT) chelating ligand via a pentyloxy spacer to phenylbenzoxazole. The fluorescent rhenium complexes 6 and 9 selectively stainined the beta-amyloid plaques on the sections of transgenic mouse, and showed high affinity for A beta((1-42)) aggregates (K-i = 11.1 nM and 14.3 nM, respectively). Autoradiography in vitro indicated that [Tc-99m]6 clearly labeled beta-amyloid plaques on the sections of transgenic mouse. Biodistribution experiments in normal mice revealed that [Tc-99m]6 displayed moderate initial brain uptake (0.81% ID/g at 2 min), and quickly washed out from the brain (0.25% ID/g at 60 min). The preliminary results indicate that the properties of [Tc-99m]6 are promising, although additional refinements are needed to improve the ability to cross the blood-brain barrier. (C) 2012 Elsevier Ltd. All rights reserved.
• 99mTc-labeled-2-arylbenzoxazole derivatives as potential Aβ imaging probes for single-photon emission computed tomography
  作者：Xuedan Wang、Mengchao Cui、Jianhua Jia、Boli Liu

  DOI：10.1016/j.ejmech.2014.10.046

  日期：2015.1

  Four neutral Tc-99m/Re-labeled 2-arylbenzoxazole derivatives conjugated to bis (aminoethanethiol) (BAT) chelating ligand via a short propoxy spacer were synthesized and evaluated. In vitro binding assay showed that they displayed binding affinities to A beta(1-42) aggregates (K-i = 15.86-393.18 nM). In vitro autoradiography studies further confirmed the high and specific binding of [Tc-99m]20 to beta-amyloid plaques on brain sections of transgenic mice. Biodistribution study of [Tc-99m]17-20 in normal mice displayed moderate initial brain uptake (0.96-1.55%ID/g at 2 min), and fast washed out from the brain (0.14-0.40%ID/g at 60 min), especially for [Tc-99m]20 with a brain(2min)/brain(60min) ratio of 8.86. Taken together, these preliminary data suggested that [Tc-99m]20 may be a potential imaging probe for detecting amyloid plaques in the brain. (C) 2014 Elsevier Masson SAS. All rights reserved.
• US9809585B2
  申请人：——

  公开号：US9809585B2

  公开（公告）日：2017-11-07
• Novel ¹⁸F-Labeled Benzoxazole Derivatives as Potential Positron Emission Tomography Probes for Imaging of Cerebral β-Amyloid Plaques in Alzheimer’s Disease
  作者：Mengchao Cui、Masahiro Ono、Hiroyuki Kimura、Masashi Ueda、Yuji Nakamoto、Kaori Togashi、Yoko Okamoto、Masafumi Ihara、Ryosuke Takahashi、Boli Liu、Hideo Saji

  DOI：10.1021/jm300251n

  日期：2012.11.8

  Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[F-18]fluoroethoxy)ethoxy)ethoxy)benzo-[d]oxazol-2-yl)-N-methylaniline ([F-18]24) and 4-(5-(2-(2-[F-18]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline ([F-18]32), were synthesized and evaluated as probes for imaging cerebral beta-amyloid (A beta) plaques in living brain tissue by PET. [F-18]24 and [F-18]32 displayed high affinity for A beta(1-42) aggregates (K-1 = 9.3 and 3.9 nM, respectively). In vitro autoradiography with sections of post-mortem AD brain and transgenic mouse brain confirmed the affinity of these tracers. Initial high uptake into and rapid washout from the brain in normal mice were observed. [F-18]24 also displayed excellent binding to A beta plaques in ex vivo autoradiographic experiments with Tg2576 mice. Furthermore, small-animal PET studies demonstrated significant differences in the clearance profile after the administration of [F-18]24 between Tg2576 and wild-type mice. The results suggest [F-18]24 to be a useful PET agent for detecting A beta plaques in the living human brain.