(E)-4-methylamino-4'-hydroxystilbene | 499786-88-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-4-methylamino-4'-hydroxystilbene
• 英文别名: 4-methylamino-4'-hydroxystilbene；4-(4-(Methylamino)styryl)phenol；4-[(E)-2-[4-(methylamino)phenyl]ethenyl]phenol
• CAS: 499786-88-8
• 化学式: C₁₅H₁₅NO
• 分子量: 225.29
• InChiKey: ZWIARAQZLULYPG-NSCUHMNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-4-methylamino-4'-hydroxystilbene 在 吡啶 、 四丁基氟化铵 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.5h， 生成 [2-(hydroxymethyl)-3-[4-[(E)-2-[4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]phenyl]ethenyl]phenoxy]propyl] 4-methylbenzenesulfonate
  参考文献：
  名称：

  F-18 Stilbenes as PET Imaging Agents for Detecting β-Amyloid Plaques in the Brain

  摘要：

  Imaging agents targeting beta-amyloid (A beta) may be useful for diagnosis and treatment of patients with Alzheimer's disease (AD). Compounds 3e and 4e are fluorinated stilbene derivatives displaying high binding affinities for A beta plaques in AD brain homogenates (K-i = 15 +/- 6 and 5.0 +/- 1.2 nM, respectively). In vivo biodistributions of [F-18]3e and [F-18]4e in normal mice exhibited excellent brain penetrations (5.55 and 9.75% dose/g at 2 min), and rapid brain washouts were observed, especially for [F-18]4e (0.72% dose/g at 60 min). They also showed in vivo plaque labeling in APP/PS1 or Tg2576 transgenic mice, animal models for AD. Autoradiography of postmortem AD brain sections and AD homogenate binding studies confirmed the selective and specific binding properties to A beta plaques. In conclusion, the preliminary results strongly suggest that these fluorinated stilbene derivatives, [F-18]3e and [(18F)]4e, are suitable candidates as A beta plaque imaging agents for studying patients with AD.

  DOI：

  10.1021/jm050166g
• 作为产物：
  描述：

  4-羟基-4'-硝基二苯乙烯 在 盐酸 、 sodium methylate 、 tin(ll) chloride 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.0h， 生成 (E)-4-methylamino-4'-hydroxystilbene
  参考文献：
  名称：

  F-18 Stilbenes as PET Imaging Agents for Detecting β-Amyloid Plaques in the Brain

  摘要：

  Imaging agents targeting beta-amyloid (A beta) may be useful for diagnosis and treatment of patients with Alzheimer's disease (AD). Compounds 3e and 4e are fluorinated stilbene derivatives displaying high binding affinities for A beta plaques in AD brain homogenates (K-i = 15 +/- 6 and 5.0 +/- 1.2 nM, respectively). In vivo biodistributions of [F-18]3e and [F-18]4e in normal mice exhibited excellent brain penetrations (5.55 and 9.75% dose/g at 2 min), and rapid brain washouts were observed, especially for [F-18]4e (0.72% dose/g at 60 min). They also showed in vivo plaque labeling in APP/PS1 or Tg2576 transgenic mice, animal models for AD. Autoradiography of postmortem AD brain sections and AD homogenate binding studies confirmed the selective and specific binding properties to A beta plaques. In conclusion, the preliminary results strongly suggest that these fluorinated stilbene derivatives, [F-18]3e and [(18F)]4e, are suitable candidates as A beta plaque imaging agents for studying patients with AD.

  DOI：

  10.1021/jm050166g

文献信息

• 2-ARYLBENZOTHIOPHENE DERIVATIVES OR PHARCEUTICALLY ACCEPTABLE SALTS THEREOF, PREPARATION METHOD THEREOF, AND PHARCEUTICAL COMPOSITION FOR THE DIAGNOSIS OR TREATMENT OF DEGENERATIVE BRAIN DISEASE CONTAINING THE SAME AS ACTIVE INGREDIENT
  申请人：Chi Dae Yoon

  公开号：US20100261727A1

  公开（公告）日：2010-10-14

  2-arylbenzothiophene derivatives or pharmaceutically acceptable salts thereof, a preparation method thereof, and a pharmaceutical composition for the diagnosis or treatment of degenerative brain disease containing the same as an active ingredient. Since the 2-arylbenzothiophene derivatives of Formula 1 have a relatively high binding affinity for β-amyloid, they can be used as diagnostic reagents for diagnosing Alzheimer's disease at an early stage by non-invasive techniques when they are labeled with radioisotopes: wherein R 1 -R 4 , V, W, X, Y and Z are as defined in the Detailed Descript of the specification. Further, when the pharmaceutical composition containing the 2-arylbenzothiophene derivative binds with a low-molecular weight β-amyloid peptide binding compound, generation of malignant high-molecular weight β-amyloid deposits is minimized. Accordingly, the pharmaceutical composition can be used as a therapeutic agent of degenerative brain disease such as Alzheimer's disease.

  2-芳基苯并噻吩衍生物或其药用可接受盐，其制备方法，以及包含其作为活性成分的用于诊断或治疗退行性脑疾病的药物组合物。由于式1中的2-芳基苯并噻吩衍生物具有相对较高的β-淀粉样蛋白结合亲和力，因此当它们与放射性同位素标记时，它们可以作为诊断试剂用于通过非侵入性技术早期诊断阿尔茨海默病： 其中R1-R4，V，W，X，Y和Z如规范的详细描述中所定义。此外，当含有2-芳基苯并噻吩衍生物的药物组合物与低分子量β-淀粉样蛋白结合化合物结合时，最小化了恶性高分子量β-淀粉样蛋白沉积物的生成。因此，该药物组合物可用作治疗阿尔茨海默病等退行性脑疾病的治疗剂。
• Synthesis of fluorescent probes based on stilbenes and diphenylacetylenes targeting β-amyloid plaques
  作者：Ajit K. Parhi、Mei-Ping Kung、Karl Ploessl、Hank F. Kung

  DOI：10.1016/j.tetlet.2008.03.130

  日期：2008.5

  Three fluorescent probes were synthesized aiming for optical imaging to detect amyloid plaques present in patients with Alzheimer's disease (AD). These compounds were prepared via Sonogashira coupling of a well-defined fluorophore (4-bora-3a, 4a-diaza s-indacene, BODIPY) with the pharmacophore possessing either a stilbene or a diphenylacetylene moiety. Different polyethylene glycol chain lengths were

  合成了三种荧光探针，旨在进行光学成像以检测阿尔茨海默病 (AD) 患者中存在的淀粉样蛋白斑块。这些化合物是通过定义明确的荧光团（4-bora-3a，4a-二氮杂茚，BODIPY）与具有二苯乙烯或二苯乙炔部分的药效团的 Sonogashira 偶联制备的。不同的聚乙二醇链长被用作荧光团和药效团之间的接头，以调整这些探针的亲脂性。这些化合物在 665-680 nm 之间表现出强烈的荧光发射，并且具有与母体荧光团 BODIPY 染料相当的非常高的消光系数。
• MULTI-TARGETING AGENTS FOR ALZHEIMER'S DISEASE THERAPY
  申请人：The Regents of the University of California

  公开号：US20200171016A1

  公开（公告）日：2020-06-04

  The disclosure provides for multi-targeting agents that assist in the targeted removal of amyloid beta plaques from the brain and surrounding vasculature of subject's with Alzheimer's disease, and methods of treatment thereof.

  该披露提供了一种多靶向药剂，可帮助定向清除患有阿尔茨海默病的受试者大脑和周围血管系统中的淀粉样蛋白斑块，并提供了相应的治疗方法。
• USE OF NOVEL COMPOUND HAVING AFFINITY FOR AMYLOID, AND PROCESS FOR PRODUCTION OF THE SAME
  申请人：Nihon Medi-Physics Co., Ltd.

  公开号：EP2218463A1

  公开（公告）日：2010-08-18

  The invention provides a reagent for detecting amyloid in a biological tissue which can be detect amyloid in vitro and in vivo with high sensitivity using a compound which has affinity with amyloid and is suppressed in toxicity such as mutagenicity. The reagent for detecting amyloid deposited in a biological tissue comprises a compound represented by the following formula (1) or a salt thereof: wherein A1, A2, A3 and A4 independently represents a carbon or nitrogen; R1 is a halogen substituent; R2 is a halogen substituent; and m is an integer or 0 to 2, provided that at least one of R1 and R2 is a radioactive halogen substituent, at least one of A1, A2, A3 and A4 represents a carbon, and R1 binds to a carbon represented by A1, A2, A3 and A4.

  该发明提供了一种用于检测生物组织中淀粉样蛋白的试剂，可以利用一种与淀粉样蛋白亲和力强且在毒性方面受到抑制（如致突变性）的化合物，在体外和体内高灵敏度地检测淀粉样蛋白。用于检测生物组织中沉积的淀粉样蛋白的试剂包括下式（1）所表示的化合物或其盐：其中A1、A2、A3和A4独立地代表碳或氮；R1是卤素取代基；R2是卤素取代基；m是整数或0到2，但至少R1和R2中的一个是放射性卤素取代基，A1、A2、A3和A4中至少一个代表碳，且R1与A1、A2、A3和A4所代表的碳结合。
• NOVEL COMPOUND WITH AMYLOID AFFINITY
  申请人：Okumura Yuki

  公开号：US20140121377A1

  公开（公告）日：2014-05-01

  A compound represented by the following formula (1), or a salt thereof: wherein R 1 is a radioactive halogen substituent, 0 to 2 of A 1 , A 2 , A 3 and A 4 represent N, and the rest represent —(CH)— is effective as a diagnostic imaging probe targeting amyloid. A diagnostic agent for Alzheimer's disease contains a compound represented by the above formula (1) or a salt thereof. After administration to a patient, the compound and the diagnostic agent for Alzheimer's disease transfer into the patient's brain, and indicate good accumulation on amyloid deposited in the brain.

  由以下公式（1）表示的化合物，或其盐：其中R1是放射性卤素取代基，A1、A2、A3和A4中的0至2个代表N，其余代表—(CH)—，作为靶向淀粉样物的诊断成像探针具有有效性。 一种用于阿尔茨海默病的诊断试剂包含上述公式（1）表示的化合物或其盐。 在向患者施用后，该化合物和用于阿尔茨海默病的诊断试剂转移到患者的大脑，并显示在大脑中沉积的淀粉上有良好的积累。