(E,E)-2,5-bis(4’-hydroxy-3’-carboxystyryl)-1-iodobenzene

• 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,E)-2,5-bis(4’-hydroxy-3’-carboxystyryl)-1-iodobenzene
• 英文别名: (E,E)-1-iodo-2,5-bis((3-hydroxycarbonyl-4-methoxy)styryl)benzene；(E,E)-1-iodo-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene；ISB；5-((E)-2-{4-[(E)-2-(3-carboxy-4-hydroxyphenyl)vinyl]-2-iodophenyl}vinyl)-2-hydroxybenzoic acid；5-[(E)-2-[4-[(E)-2-(3-carboxy-4-hydroxyphenyl)ethenyl]-3-iodophenyl]ethenyl]-2-hydroxybenzoic acid
• 化学式: C₂₄H₁₇IO₆
• 分子量: 528.3
• InChiKey: ITFHEGXMRYCTLF-WMWQKROPSA-N

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

• 作为反应物：
  描述：

  (E,E)-2,5-bis(4’-hydroxy-3’-carboxystyryl)-1-iodobenzene 在 sodium tetrahydroborate 、 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.58h， 以85%的产率得到(E,E)-2,5-bis(4’-hydroxy-3’-carboxystyryl)benzene
  参考文献：
  名称：

  Tritium-labeled (E,E)-2,5-bis(4′-hydroxy-3′-carboxystyryl)benzene as a probe for β-amyloid fibrils

  摘要：

  Accumulation of A beta in the brains of Alzheimer disease (AD) patients reflects an imbalance between A beta production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid A beta 40 and A beta 42 peptides that assemble into fibrils and form plaques. Plaque-buildup occurs over an extended time-frame, and the early detection and modulation of plaque formation are areas of active research. Radiolabeled probes for the detection of amyloid plaques and fibrils in living subjects are important for noninvasive evaluation of AD diagnosis, progression, and differentiation of AD from other neurode-generative diseases and age-related cognitive decline. Tritium-labeled (E, E)-1-[H-3]-2,5-bis(4'-hydroxy-3'-carbomethoxystyryl)benzene possesses an improved level of chemical stability relative to a previously reported radioiodinated analog for radiometric quantification of A beta plaque and tau pathology in brain tissue and in vitro studies with synthetic A beta and tau fibrils. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.09.075
• 作为产物：
  描述：

  1,4-二甲基-2-碘苯 在 吡啶 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 水 、 sodium methylate 、 三溴化硼 、 sodium hydroxide 作用下， 以 甲醇 、 四氯化碳 、 乙醇 、 二氯甲烷 为溶剂， 反应 188.0h， 生成 (E,E)-2,5-bis(4’-hydroxy-3’-carboxystyryl)-1-iodobenzene
  参考文献：
  名称：

  Tritium-labeled (E,E)-2,5-bis(4′-hydroxy-3′-carboxystyryl)benzene as a probe for β-amyloid fibrils

  摘要：

  Accumulation of A beta in the brains of Alzheimer disease (AD) patients reflects an imbalance between A beta production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid A beta 40 and A beta 42 peptides that assemble into fibrils and form plaques. Plaque-buildup occurs over an extended time-frame, and the early detection and modulation of plaque formation are areas of active research. Radiolabeled probes for the detection of amyloid plaques and fibrils in living subjects are important for noninvasive evaluation of AD diagnosis, progression, and differentiation of AD from other neurode-generative diseases and age-related cognitive decline. Tritium-labeled (E, E)-1-[H-3]-2,5-bis(4'-hydroxy-3'-carbomethoxystyryl)benzene possesses an improved level of chemical stability relative to a previously reported radioiodinated analog for radiometric quantification of A beta plaque and tau pathology in brain tissue and in vitro studies with synthetic A beta and tau fibrils. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.09.075

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：——
• Tritium-labeled (E,E)-2,5-bis(4′-hydroxy-3′-carboxystyryl)benzene as a probe for β-amyloid fibrils
  作者：Sergey V. Matveev、Stefan Kwiatkowski、Vitaliy M. Sviripa、Robert C. Fazio、David S. Watt、Harry LeVine

  DOI：10.1016/j.bmcl.2014.09.075

  日期：2014.12

  Accumulation of A beta in the brains of Alzheimer disease (AD) patients reflects an imbalance between A beta production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid A beta 40 and A beta 42 peptides that assemble into fibrils and form plaques. Plaque-buildup occurs over an extended time-frame, and the early detection and modulation of plaque formation are areas of active research. Radiolabeled probes for the detection of amyloid plaques and fibrils in living subjects are important for noninvasive evaluation of AD diagnosis, progression, and differentiation of AD from other neurode-generative diseases and age-related cognitive decline. Tritium-labeled (E, E)-1-[H-3]-2,5-bis(4'-hydroxy-3'-carbomethoxystyryl)benzene possesses an improved level of chemical stability relative to a previously reported radioiodinated analog for radiometric quantification of A beta plaque and tau pathology in brain tissue and in vitro studies with synthetic A beta and tau fibrils. (C) 2014 Elsevier Ltd. All rights reserved.