2-(4’-chloroacetamide-phenyl)-6-methoxybenzothiazole | 1159301-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-(4’-chloroacetamide-phenyl)-6-methoxybenzothiazole
• CAS: 1159301-83-3
• 化学式: C₁₆H₁₃ClN₂O₂S
• 分子量: 332.81
• InChiKey: LPEOUEZMNOZOBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.15
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  51.22
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-(4’-chloroacetamide-phenyl)-6-methoxybenzothiazole 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 2-(4’-chloroacetamide-phenyl)-6-metoxybenzothiazol-DO3A
  参考文献：
  名称：

  与匹兹堡化合物B共轭的Gd 3+复合物：β-淀粉样蛋白斑的潜在MRI标记

  摘要：

  摘要为了通过T 1加权磁共振成像来可视化β淀粉样蛋白（Aβ）斑块以检测阿尔茨海默氏病，我们报告了三种不同的1,4,7稳定，不带电的Gd 3+复合物的合成和表征与匹兹堡化合物B共轭的1,10-四氮杂环十二烷-1,4,7-三乙酸单酰胺衍生物，是公认的Aβ斑块标记。配体L 1，L 2和L 3连接大环螯合剂和匹兹堡化合物B靶向部分的间隔基的性质和大小不同，这会影响它们的亲脂性，配合物的辛醇-水分配系数范围为-0.15至0.32。考虑到它们的两亲行为，这些络合物在水溶液中形成胶束（临界胶束浓度为1.00-1.49 mM）。通过结合的17 O NMR和1来评估确定弛豫性的参数，包括水交换速率和旋转相关时间，用于单体和胶束形式H核磁弛豫弥散（NMRD）研究。它们很大程度上受接头的聚集状态和疏水特性影响。使用Lipari-Szabo方法对局部状态和全局运动对聚合状态的旋转动力学的分析表明，该聚合状态非常灵

  DOI：

  10.1007/s00775-013-1055-8
• 作为产物：
  描述：

  2-氨基-5-甲氧基苯硫酚 在 乙醇 、 potassium carbonate 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 2-(4’-chloroacetamide-phenyl)-6-methoxybenzothiazole
  参考文献：
  名称：

  Design, synthesis and structure–activity relationship of rhenium 2-arylbenzothiazoles as β-amyloid plaque binding agents

  摘要：

  To continue our efforts toward the development of Tc-99m PiB analogs, we have synthesized 24 neutral and lipophilic Re (as a surrogate of Tc-99m) 2-arylbenzothiazoles, and explored their structure-activity relationship for binding to A beta(1-40) fibrils. These Re complexes were designed and synthesized via the integrated approach, so their 99mTc analogs would have a greater chance of crossing the blood-brain barrier. While the lipophilicities (logP(C18) = 1.59-3.53) of these Re 2-arylbenzothiazoles were all within suitable range, their binding affinities (K-i = 30-617 nM) to A beta(1-40) fibrils varied widely depending on the selection and integration of the tetradentate chelator into the 2-phenylbenzothiazole pharmacophore. For potential clinical applications, further refinement to obtain Re 2-arylbenzothiazoles with better binding affinities (<10 nM) will likely be needed. The integrated approach reported here to generate compact, neutral and lipophilic Re 2-arylbenzothiazoles could be applied to other potent pharmacophores as well to convert other current Ab PET tracers to their Tc-99m analogs for more widespread application via the use of SPECT scanners. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.068

文献信息

• Synthesis and β-amyloid binding properties of rhenium 2-phenylbenzothiazoles
  作者：Kuo-Shyan Lin、Manik L. Debnath、Chester A. Mathis、William E. Klunk

  DOI：10.1016/j.bmcl.2009.02.096

  日期：2009.4

  As a first step toward the development of (99m)Tc PiB analogs, we have synthesized six neutral Re 2-phenylbenzothiazoles via pendant or integrated approach. These Re compounds bind to A beta(1-40) fibrils with fairly good affinities (K(i) = 10.0-88.6 nM) and have moderate lipophilicities (logP(C18) = 1.21-3.26). The Re compounds prepared via the integrated approach are smaller in size, and therefore their corresponding 99mTc analogs would have a greater chance of crossing the blood-brain barrier well. For potential clinical applications, further optimization on the structure-activity relationship to obtain Re 2-phenylbenzothiazoles with higher binding affinities (< 10 nM) might be needed. The integrated approach reported here to obtain neutral, compact and lipophilic Re 2-phenylbenzothiazoles could to be applied to other high affinity pharmacophores as well as to generate (99m)Tc analogs that could hold promise for extending the use of Ab imaging in living human brain to many more clinical settings because they could be used with SPECT. (c) 2009 Elsevier Ltd. All rights reserved.
• PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the Visualization of β-Amyloid Plaques
  作者：André F. Martins、Jean-François Morfin、Anna Kubíčková、Vojtěch Kubíček、Frédéric Buron、Franck Suzenet、Milena Salerno、Adina N. Lazar、Charles Duyckaerts、Nicolas Arlicot、Denis Guilloteau、Carlos F. G. C. Geraldes、Éva Tóth

  DOI：10.1021/ml400042w

  日期：2013.5.9

  In an effort toward the visualization of beta-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a well-established marker of Afi plaques, to DO3A-monoamide that is capable of forming stable, noncharged complexes with different trivalent metal ions including Gd3+ for MRI and In-111(3+). for SPECT applications. Proton relaxivity measurements evidenced binding of Gd(DO3A-PiB) to the amyloid peptide A beta(1-40) and to human serum albumin, resulting in a two- and four-fold relaidvity increase, respectively. Ex vivo immunohistochemical studies showed that the DO3A-PiB complexes selectively target A beta plaques on Alzheimer's disease human brain tissue. Ex vivo biodistribution data obtained for the In-111-analogue pointed to a moderate blood-brain barrier (BBB) penetration in adult male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min postinjection.