1-溴-2,5-二(3-羧基-4-羟基苯乙烯基)苯 | 291766-06-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 1-溴-2,5-二(3-羧基-4-羟基苯乙烯基)苯
• 英文名称: (E,E)-1-bromo-2,5-bis(3-hydroxycarbonyl-4-hydroxystyryl)benzene
• 英文别名: (E,E)-2,5-bis(4’-hydroxy-3’-carboxystyryl)-1-bromobenzene；(trans,trans)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene；1-Bromo-2,5-bis(3-carboxy-4-hydroxystyryl)benzene；5-[(E)-2-[3-bromo-4-[(E)-2-(3-carboxy-4-hydroxyphenyl)ethenyl]phenyl]ethenyl]-2-hydroxybenzoic acid
• CAS: 291766-06-8
• 化学式: C₂₄H₁₇BrO₆
• 分子量: 481.299
• InChiKey: ZVECSLHUCRIBDY-WMWQKROPSA-N

物化性质

• 沸点：
  705.5±60.0 °C(Predicted)
• 密度：
  1.637±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：100 mg/mL（207.77 mM；超声加热并加热至 60°C）

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  115
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-溴-1,4-双(溴甲基)苯 在 氢氧化钾 、 sodium methylate 、 三溴化硼 作用下， 以 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 1-溴-2,5-二(3-羧基-4-羟基苯乙烯基)苯
  参考文献：
  名称：

  Radioiodinated Styrylbenzenes and Thioflavins as Probes for Amyloid Aggregates

  摘要：

  We report for the first time that small molecule-based radiodiodinated ligands, showing selective binding to A beta aggregates, cross the intact blood-brain barrier by simple diffusion. Four novel ligands showing preferential labeling of amyloid aggregates of A beta (1-40) and A beta (1-42) peptides, commonly associated with plaques in the brain of people with Alzheimer's disease (AD), were developed. Two I-125-labeled styrylbenzenes, (E,E)-1-iodo-2,5-bis(3-hydroxycarbonyl-4-hydroxy)-styrylbenzene, 12 (ISB), and (E,E)-1-iodo-2,5-bis(3-hydroxycarbonyl-4-methoxy)styrylbenzene, 13 (IMSB), and two I-125-labeled thioflavins, 2-[4 '-(dimethylamino)phenyl]-6-iodobenzothiazole, 18a (TZDM), and 2- [4 '-(4 " -methylpiperazin-1-yl)phenyl]-6-iodobenzothiazole, 18b (TZPI), were prepared at a high specific activity (2200 Ci/mmol). In vitro binding studies of these ligands showed excellent binding affinities with K-d values of 0.08, 0.13, 0.06, and 0.13 nM for aggregates of A beta (1-40) and 0.15, 0.73, 0.14, and 0.15 nM for aggregates of A beta (1-42), respectively. Interestingly, under a competitive-binding assaying condition, different binding sites on A beta (1-40) and A beta (1-42) aggregates, which are mutually exclusive, were observed for styrylbenzenes and thioflavins. Autoradiography studies of postmortem brain sections of a patient with Down's syndrome known to contain primarily A beta (1-42) aggregates in the brain showed that both [I-125]18a and [I-125]18b labeled these brain sections, but [I-125]13, selective for A beta (1-40) aggregates, exhibited very low labeling of the comparable brain section. Biodistribution studies in normal mice after an iv injection showed that [I-125]18a and [I-125]18b exhibited excellent brain uptake and retention, the levels of which were much higher than those of [I-125]12 and [I-125]13. These findings strongly suggest that the new radioiodinated ligands, [I-125]12 (ISB), [I-125]13 (IMSB), [I-125]18a, (TZDM), and [I-125]18b (TZPI), may be useful as biomarkers for studying A beta (1-40) as well as A beta (1-42) aggregates of amyloidogenesis in AD patients.

  DOI：

  10.1021/jm010045q

文献信息

• Radioiodinated Styrylbenzenes and Thioflavins as Probes for Amyloid Aggregates
  作者：Z.-P. Zhuang、M.-P. Kung、C. Hou、D. M. Skovronsky、T. L. Gur、K. Plössl、J. Q. Trojanowski、V. M.-Y. Lee、H. F. Kung

  DOI：10.1021/jm010045q

  日期：2001.6.1

  We report for the first time that small molecule-based radiodiodinated ligands, showing selective binding to A beta aggregates, cross the intact blood-brain barrier by simple diffusion. Four novel ligands showing preferential labeling of amyloid aggregates of A beta (1-40) and A beta (1-42) peptides, commonly associated with plaques in the brain of people with Alzheimer's disease (AD), were developed. Two I-125-labeled styrylbenzenes, (E,E)-1-iodo-2,5-bis(3-hydroxycarbonyl-4-hydroxy)-styrylbenzene, 12 (ISB), and (E,E)-1-iodo-2,5-bis(3-hydroxycarbonyl-4-methoxy)styrylbenzene, 13 (IMSB), and two I-125-labeled thioflavins, 2-[4 '-(dimethylamino)phenyl]-6-iodobenzothiazole, 18a (TZDM), and 2- [4 '-(4 " -methylpiperazin-1-yl)phenyl]-6-iodobenzothiazole, 18b (TZPI), were prepared at a high specific activity (2200 Ci/mmol). In vitro binding studies of these ligands showed excellent binding affinities with K-d values of 0.08, 0.13, 0.06, and 0.13 nM for aggregates of A beta (1-40) and 0.15, 0.73, 0.14, and 0.15 nM for aggregates of A beta (1-42), respectively. Interestingly, under a competitive-binding assaying condition, different binding sites on A beta (1-40) and A beta (1-42) aggregates, which are mutually exclusive, were observed for styrylbenzenes and thioflavins. Autoradiography studies of postmortem brain sections of a patient with Down's syndrome known to contain primarily A beta (1-42) aggregates in the brain showed that both [I-125]18a and [I-125]18b labeled these brain sections, but [I-125]13, selective for A beta (1-40) aggregates, exhibited very low labeling of the comparable brain section. Biodistribution studies in normal mice after an iv injection showed that [I-125]18a and [I-125]18b exhibited excellent brain uptake and retention, the levels of which were much higher than those of [I-125]12 and [I-125]13. These findings strongly suggest that the new radioiodinated ligands, [I-125]12 (ISB), [I-125]13 (IMSB), [I-125]18a, (TZDM), and [I-125]18b (TZPI), may be useful as biomarkers for studying A beta (1-40) as well as A beta (1-42) aggregates of amyloidogenesis in AD patients.
• Zhuang, Z.-P.; Kung, M.-P.; Hou, C., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S236 - S238
  作者：Zhuang, Z.-P.、Kung, M.-P.、Hou, C.、Lee, C.-W.、Trojanowski, J. Q.、Lee, V. M.-Y.、Kung, H. F.

  DOI：——

  日期：——
• Isomerization of (<i>Z</i>,<i>Z</i>) to (<i>E</i>,<i>E</i>)1-Bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene in Strong Base:  Probes for Amyloid Plaques in the Brain
  作者：Chi-Wan Lee、Zhi-Ping Zhuang、Mei-Ping Kung、Karl Plössl、Daniel Skovronsky、Tamar Gur、Catherine Hou、John Q. Trojanowski、Virginia M.-Y. Lee、Hank F. Kung

  DOI：10.1021/jm010161t

  日期：2001.7.1

  In developing probes for detecting beta -amyloid (A beta) plaques in the brain of Alzheimer's disease (AD), we have synthesized 1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (5, BSB). Due to the presence of two double bonds, formation of four different isomers is possible. Four isomers, E,E-5, E,Z-5, Z,E-5, and Z,Z-5, were prepared. Surprisingly, all showed strong fluorescent labeling of A beta plaques in the brain of postmortem brain sections of patients with confirmed AD. In vitro binding assay also showed that all four isomers of BSB (E,E-5, E,Z-5, Z,E-5, and Z,Z-5) displayed a similar high binding affinity inhibiting the binding of [I-125]E,E, 6, 1-iodo-2,5-bis-(3-hydroxycarbonyl-4-methoxy)styrylbenzene (IMSB) to A beta (1-40) aggregates. The inhibition constants (K-i) of E,E-5, E,Z-5, E,Z-5, and Z,Z-5 were 0.11 +/- 0.01, 0.19 +/- 0.03, 0.27 +/- 0.06, and 0.13 +/- 0.02 nM, respectively. Due to the fact that geometric stability of these styrylbenzenes is unknown, and the conversion of Z,Z-5 to E,E-5 may occur automatically in the binding or labeling assaying conditions, we have investigated the kinetics of conversion of Z,Z-5 to E,E-5 by NMR in D2O/NaOD at elevated temperatures (70, 95, and 115 degreesC). The activation energy was determined to be 14.15 kcal/mol. The results strongly suggest that the isomeric conversion at room temperature in aqueous buffer solution is unlikely. All of the styrylbenzene isomers clearly showed potential as useful tools for studying A beta aggregates in the brain. The data suggest that, despite the rigidity of this series of styrylbenzenes, the binding sites on A beta aggregates may have certain flexibility and the binding pockets could be adaptable for binding to other smaller ligands. Such information could be exploited to develop new ligands for detecting amyloid plaques in AD.
• METHODS AND COMPOSITIONS FOR DECOMPOSITION OF BIOMASS
  申请人：Aurora Rajeev

  公开号：US20130034888A1

  公开（公告）日：2013-02-07

  Disclosed are methods for detecting cellulose in cellulosic materials and producing alcohol using cellulosic materials. More particularly, disclosed are methods for producing alcohol in a cell-free system by contacting pyruvate with enzymes from a minimal enzymatic pathway. Also disclosed are methods of producing pyruvate by culturing a microorganism under hypoxic conditions. Disclosed are methods for detecting cellulose in a sample using Congo red dye.
• PET MONITORING OF A-BETA-DIRECTED IMMUNOTHERAPY
  申请人：Black Ronald

  公开号：US20130084245A1

  公开（公告）日：2013-04-04

  The present invention provides methods of monitoring Aβ-directed immunotherapy. The methods involve administering a PET ligand that binds to amyloid deposits and detecting the PET ligand in the brain to provide an indication of the level and/or distribution of amyloid deposits. Surprisingly, the data in the present application show that a statistically significant reduction in amyloid deposits occurs early and consistently among patients following initiation of treatment before statistically significant effects of most if not all other markers are detectable. In consequence, the present methods allow early detection of whether a patient is responding to the Aβ-directed immunotherapy and if necessary adjustment of the immunotherapy regime.