5‑methoxy‑2‑(4‑aminophenyl)benzofuran | 888703-98-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 2-芳基苯并呋喃类黄酮
• 英文名称: 5‑methoxy‑2‑(4‑aminophenyl)benzofuran
• 英文别名: 5-Methoxy-2-(4-aminophenyl)benzofuran；4-(5-methoxy-1-benzofuran-2-yl)aniline
• CAS: 888703-98-8
• 化学式: C₁₅H₁₃NO₂
• 分子量: 239.274
• InChiKey: GICMHQJTKXNMGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  48.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5‑methoxy‑2‑(4‑aminophenyl)benzofuran 在 咪唑 、 sodium methylate 、 三溴化硼 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 tert-butyl 4-(5-(2-(2-(2-(tert-butyldimethylsilyloxy)ethoxy)ethoxy)ethoxy)benzofuran-2-yl)phenyl-N-methylcarbamate
  参考文献：
  名称：

  Novel ¹⁸F-Labeled Benzofuran Derivatives with Improved Properties for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques in Alzheimer’s Brains

  摘要：

  In vivo imaging of beta-amyloid plaques in the brain may lead to the early diagnosis of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. In the present study, we report on the development two potential PET probes, [F-18]FPYBF-2 ([F-18]10) and [F-18]FPHBF-2 ([F-18]21), for imaging of beta-amyloid plagues in AD brain. In experiments in vitro, 10 and 21 displayed high affinity for A beta(1-42) aggregates (K-i = 2.41 and 3.85 nM, respectively). In biodistribution experiments using normal mice, they displayed high uptake in the brain (7.38 and 8.18% ID/g at 2 mm postinjection,, respectively), and the radioactivity washed out from the, brain rapidly (3.15 and 3.87% ID/g at 60 min postinjection, respectively), which is highly desirable for beta-amyloid imaging agents. In vivo, they clearly labeled beta-amyloid plaques in Tg2576 mice. Furthermore, the specific labeling of beta-amyloid plaques by 10 and 21 was observed in autoradiographs of sections of autopsied AD brain. These new fluorinated benzofuran derivatives are promising PET probes for imaging cerebral beta-amyloid plaques.

  DOI：

  10.1021/jm200057u
• 作为产物：
  描述：

  2-羟基-5-甲氧基苯甲醛 在 sodium tetrahydroborate 、 三乙胺 、 tin(ll) chloride 作用下， 以 乙醇 、 甲苯 、 乙腈 为溶剂， 反应 6.0h， 生成 5‑methoxy‑2‑(4‑aminophenyl)benzofuran
  参考文献：
  名称：

  新型苯并呋喃衍生物，用于在阿尔茨海默氏病大脑中对β-淀粉样蛋白斑进行PET成像。

  摘要：

  合成和评估了一系列新型的苯并呋喃衍生物，作为针对阿尔茨海默病（AD）中淀粉样蛋白斑的潜在正电子发射断层扫描（PET）示踪剂。三苯基phosph盐和4-硝基苯甲酰氯之间的分子内维蒂希反应成功地完成了苯并呋喃的合成。当使用一系列苯并呋喃衍生物进行使用AD脑灰质匀浆的体外结合研究时，所有检查的衍生物均显示出亚纳摩尔范围内K（i）值的高结合亲和力。在这些苯并呋喃衍生物中，化合物8、5-羟基-2-（4-甲基氨基苯基）苯并呋喃显示出最低的K（i）值（0.7 nM）。用化合物8对AD切片进行体外荧光标记不仅对淀粉样蛋白斑块，而且对神经原纤维缠结都进行了强烈染色。通过使正甲基前体5-羟基-2-（4-氨基苯基）苯并呋喃与[（11）C]三氟甲磺酸甲酯反应，制备（11）C标记的化合物8 [[（11）C] 8]。[（11）C] 8表现出中等的亲脂性（log P = 2.36），非常好的脑渗透性（在小鼠静脉内注射后2分钟时为4

  DOI：

  10.1021/jm051176k

文献信息

• Synthesis of Benzo[<i>b</i>]furans by Intramolecular C–O Bond Formation Using Iron and Copper Catalysis
  作者：Martyn C. Henry、Andrew Sutherland

  DOI：10.1021/acs.orglett.0c00754

  日期：2020.4.3

  synthesis of benzo[b]furans from 1-aryl- or 1-alkylketones using nonprecious transition metal catalysts have been developed. Regioselective iron(III)-catalyzed halogenation of the aryl ring, followed by iron- or copper-catalyzed O-arylation allowed the synthesis of various structural analogues, including the benzo[b]furan-derived natural products corsifuran C, moracin F, and caleprunin B.

  已经开发出使用非贵金属过渡金属催化剂从1-芳基酮或1-烷基酮合成苯并[ b ]呋喃的一锅法。区域选择性铁(III)催化的芳环卤化，然后是铁或铜催化的O-芳基化，可以合成各种结构类似物，包括苯并[ b ]呋喃衍生的天然产物corsifuran C、moracin F和卡普鲁宁 B.
• Novel Benzofuran Derivatives for PET Imaging of β-Amyloid Plaques in Alzheimer's Disease Brains
  作者：Masahiro Ono、Hidekazu Kawashima、Akemi Nonaka、Tomoki Kawai、Mamoru Haratake、Hiroshi Mori、Mei-Ping Kung、Hank F. Kung、Hideo Saji、Morio Nakayama

  DOI：10.1021/jm051176k

  日期：2006.5.1

  homogenates were carried out with a series of benzofuran derivatives, all the derivatives examined displayed high binding affinities with K(i) values in the subnanomolar range. Among these benzofuran derivatives, compound 8, 5-hydroxy-2-(4-methyaminophenyl)benzofuran, showed the lowest K(i) value (0.7 nM). In vitro fluorescent labeling of AD sections with compound 8 intensely stained not only amyloid plaques

  合成和评估了一系列新型的苯并呋喃衍生物，作为针对阿尔茨海默病（AD）中淀粉样蛋白斑的潜在正电子发射断层扫描（PET）示踪剂。三苯基phosph盐和4-硝基苯甲酰氯之间的分子内维蒂希反应成功地完成了苯并呋喃的合成。当使用一系列苯并呋喃衍生物进行使用AD脑灰质匀浆的体外结合研究时，所有检查的衍生物均显示出亚纳摩尔范围内K（i）值的高结合亲和力。在这些苯并呋喃衍生物中，化合物8、5-羟基-2-（4-甲基氨基苯基）苯并呋喃显示出最低的K（i）值（0.7 nM）。用化合物8对AD切片进行体外荧光标记不仅对淀粉样蛋白斑块，而且对神经原纤维缠结都进行了强烈染色。通过使正甲基前体5-羟基-2-（4-氨基苯基）苯并呋喃与[（11）C]三氟甲磺酸甲酯反应，制备（11）C标记的化合物8 [[（11）C] 8]。[（11）C] 8表现出中等的亲脂性（log P = 2.36），非常好的脑渗透性（在小鼠静脉内注射后2分钟时为4
• Novel Benzofurans with ^99mTc Complexes as Probes for Imaging Cerebral β-Amyloid Plaques
  作者：Masahiro Ono、Yasufumi Fuchi、Takeshi Fuchigami、Nobuya Kobashi、Hiroyuki Kimura、Mamoru Haratake、Hideo Saji、Morio Nakayama

  DOI：10.1021/ml100140d

  日期：2010.11.11

  Two novel benzofuran derivatives coupled with Tc-99m complexes were tested as probes for imaging cerebral beta-amyloid plaques using single photon emission tomography. Although both derivatives bound to A beta(1-42) aggregates, Tc-99m-BAT-BF showed higher affinity than. Tc-99m-MAMA-BF. In sections of brain tissue from an animal model of AD, Tc-99m-BAT-BF clearly labeled beta-amyloid plaques in biodistribution experiments using normal mice Tc-99m-BAT-BF displayed high uptake soon after its injection and washed out from the brain rapidly, a highly desirable feature for an imaging agent. Tc-99m-BAT-BF may be a potential probe for imaging beta-amyloid plaques in Alzheimer's brains.
• Novel ¹⁸F-Labeled Benzofuran Derivatives with Improved Properties for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques in Alzheimer’s Brains
  作者：Masahiro Ono、Yan Cheng、Hiroyuki Kimura、Mengchao Cui、Shinya Kagawa、Ryuichi Nishii、Hideo Saji

  DOI：10.1021/jm200057u

  日期：2011.4.28

  In vivo imaging of beta-amyloid plaques in the brain may lead to the early diagnosis of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. In the present study, we report on the development two potential PET probes, [F-18]FPYBF-2 ([F-18]10) and [F-18]FPHBF-2 ([F-18]21), for imaging of beta-amyloid plagues in AD brain. In experiments in vitro, 10 and 21 displayed high affinity for A beta(1-42) aggregates (K-i = 2.41 and 3.85 nM, respectively). In biodistribution experiments using normal mice, they displayed high uptake in the brain (7.38 and 8.18% ID/g at 2 mm postinjection,, respectively), and the radioactivity washed out from the, brain rapidly (3.15 and 3.87% ID/g at 60 min postinjection, respectively), which is highly desirable for beta-amyloid imaging agents. In vivo, they clearly labeled beta-amyloid plaques in Tg2576 mice. Furthermore, the specific labeling of beta-amyloid plaques by 10 and 21 was observed in autoradiographs of sections of autopsied AD brain. These new fluorinated benzofuran derivatives are promising PET probes for imaging cerebral beta-amyloid plaques.
• Multistep synthesis of a novel copper complex with potential for Alzheimer’s disease diagnosis
  作者：Fatma Dellal、Diego Santo Domingo Porqueras、Stacy Narayanin-Richenapin、Marine Thimotee、Vanessa Delahaye、Yacine Diouf、Karolina Piasta、Elżbieta Gumienna-Kontecka、Henryk Kozlowski、Maryline Beyler、Raphael Tripier、Alban Moyeux、Olivier Gager、Valérie Besnard、Milena Salerno

  DOI：10.1007/s00775-023-02028-8

  日期：——

  cyclam-based ligand with a moiety capable of recognizing Aβ plaques via a successful and challenging Buchwald-Hartwig coupling reaction. To our knowledge, it is the first time that such a strategy is used to functionalize polyazamacrocyclic derivatives. The thermodynamic stability constants determined in MeOH/H2O solvent indicate that the attachment of this moiety does not weaken the chelating properties

  Aβ 斑块的正电子发射断层扫描 (PET) 成像被认为是诊断阿尔茨海默病的工具。作为对疾病早期诊断新策略开发的贡献，利用 PET 医学成像技术，通过十个步骤合成了一种新的铜络合物 [Cu(TE1PA-ONO)] + 。我们策略的关键步骤是通过成功且具有挑战性的 Buchwald-Hartwig 偶联反应，将单吡啶-N-烷基化环环酰胺基配体与能够识别 Aβ 斑块的部分偶联。据我们所知，这是首次使用这种策略来功能化多氮杂大环衍生物。在MeOH/H 2 O溶剂中测定的热力学稳定常数表明该部分的连接不会削弱TE1PA-ONO配体相对于母体HTE1PA的螯合特性。这里描述的新型复合物能够识别阿尔茨海默病患者脑切片中的淀粉样斑块，并且对人类神经元细胞显示出低毒性。  图文摘要