2-[4-(2-fluoroethoxy)phenyl]-6-iodoimidazo[1,2-a]pyridine | 958641-70-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[4-(2-fluoroethoxy)phenyl]-6-iodoimidazo[1,2-a]pyridine
• 英文别名: 2-[4'-(2''-Fluoroethoxy)phenyl]-6-iodoimidazo[1,2-a]pyridine
• CAS: 958641-70-8
• 化学式: C₁₅H₁₂FIN₂O
• 分子量: 382.176
• InChiKey: PKFSXKBYBLYCAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  26.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[4-(2-fluoroethoxy)phenyl]-6-iodoimidazo[1,2-a]pyridine 、 六正丁基二锡 在 四(三苯基膦)钯 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 21.5h， 以55.4%的产率得到2-[4′-(2-fluoroethoxy)phenyl]-6-tributylstannylimidazo[1,2-a]-pyridine
  参考文献：
  名称：

  Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging β-Amyloid in Alzheimer’s Disease Affected Brain

  摘要：

  In this study, we synthesized of a series of 2phenyl- and 2-pyridyl-imidazo[1,2-a]pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of beta-amyloid (A beta). Among the 11 evaluated compounds, 10 showed moderate affinity to A beta(1-42) aggregates, exhibiting half-maximal inhibitory concentrations (IC50) of 14.7 +/- 6.07-87.6 +/- 39.8 nM. In vitro autoradiography indicated that 1231 labeled triazole-substituted derivatives displayed highly selective binding to A beta plaques in the hippocampal region of Alzheimer's disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all I-123-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging A beta plaques, with the highest selectivity observed for a 1H-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [I-123]ABC577. This compound showed good kinetics in rat brain as well as moderate in vivo stability in rats and is thus a promising SPECT imaging probe for AD in clinical settings.

  DOI：

  10.1021/acschemneuro.8b00064
• 作为产物：
  描述：

  2-溴-4'-羟基苯乙酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.5h， 生成 2-[4-(2-fluoroethoxy)phenyl]-6-iodoimidazo[1,2-a]pyridine
  参考文献：
  名称：

  Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging β-Amyloid in Alzheimer’s Disease Affected Brain

  摘要：

  In this study, we synthesized of a series of 2phenyl- and 2-pyridyl-imidazo[1,2-a]pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of beta-amyloid (A beta). Among the 11 evaluated compounds, 10 showed moderate affinity to A beta(1-42) aggregates, exhibiting half-maximal inhibitory concentrations (IC50) of 14.7 +/- 6.07-87.6 +/- 39.8 nM. In vitro autoradiography indicated that 1231 labeled triazole-substituted derivatives displayed highly selective binding to A beta plaques in the hippocampal region of Alzheimer's disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all I-123-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging A beta plaques, with the highest selectivity observed for a 1H-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [I-123]ABC577. This compound showed good kinetics in rat brain as well as moderate in vivo stability in rats and is thus a promising SPECT imaging probe for AD in clinical settings.

  DOI：

  10.1021/acschemneuro.8b00064

文献信息

• Compounds for non-invasive measurement of aggregates of amyloid peptides
  申请人：Technische Universität München

  公开号：EP2218464A1

  公开（公告）日：2010-08-18

  The invention relates to the provision of compounds, methods for producing them, and their use for imaging and quantification of aggregates of amyloid peptides in vivo. In a preferred aspect of the invention, a tracer is administered to humans and displays enrichment in the areas that are containing amyloid plaques. Tracers of the invention can be used for in vivo visualization and quantification of aggregates of amyloid peptides in patients affected diseases characterized in the generation of aggregates of amyloid peptides, for example familial or sporadic Alzheimer's disease and type II diabetes. Tracers of the invention can be used for monitoring effects of amyloid-modulating therapies of patients affected with diseases characterized in the generation of aggregates of amyloid peptides, for example familial or sporadic Alzheimer's disease and type II diabetes.

  该发明涉及化合物的提供、生产方法以及它们在体内成像和定量淀粉样肽聚集物的用途。在该发明的一个优选方面，向人类施用一种示踪剂，并且在含有淀粉样斑块的区域显示富集。该发明的示踪剂可用于患有以生成淀粉样肽聚集物为特征的疾病的患者体内成像和定量，例如家族性或散发性阿尔茨海默病和2型糖尿病。该发明的示踪剂可用于监测患有以生成淀粉样肽聚集物为特征的疾病的患者对调节淀粉样蛋白的疗法的影响，例如家族性或散发性阿尔茨海默病和2型糖尿病。
• 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 Having Affinity for Amyloid
  申请人：Tanifuji Shigeyuki

  公开号：US20090252679A1

  公开（公告）日：2009-10-08

  The present invention provides a compound which has affinity with amyloid, shows sufficiently rapid clearance from normal tissues and is suppressed in toxicity such as mutagencity. Provided is a compound represented by the following formula (1) or a salt thereof: wherein A 1 , A 2 , A 3 and A 4 independently represents a carbon or nitrogen; R 1 is a halogen substituent; R 2 is a halogen substituent; and m is an integer of 0 to 2, provided that at least one of R 1 and R 2 is a radioactive halogen substituent, at least one of A 1 , A 2 , A 3 and A 4 represents a carbon, and R 1 binds to a carbon represented by A 1 , A 2 , A 3 or A 4 as well as a low-toxic diagnostic agent comprising a compound represented by the preceding formula or a salt thereof.

  本发明提供了一种与淀粉样蛋白亲和力强，从正常组织中清除速度足够快且毒性（如诱变性）被抑制的化合物。所提供的化合物由以下公式（1）或其盐所表示：其中，A1、A2、A3和A4独立地表示碳或氮；R1是卤素取代基；R2是卤素取代基；m是0到2的整数，但至少其中一个R1和R2是放射性卤素取代基，至少一个A1、A2、A3和A4表示碳，且R1与由A1、A2、A3或A4表示的碳结合，以及包含由上述公式或其盐所表示的低毒性诊断剂。
• Compounds for Non-Invasive Measurement of Aggregates of Amyloid Peptides
  申请人：Gjermund Henriksen

  公开号：US20120070374A1

  公开（公告）日：2012-03-22

  The invention relates to the provision of compounds, methods for producing them, and their use for imaging and quantification of aggregates of β-amyloid peptides in vivo. In a preferred aspect of the invention, a tracer is administered to humans and displays enrichment in body parts that are containing aggregates of amyloid peptides. Tracers of the invention can be used for non-invasive depiction and quantification of aggregates of β-amyloid peptides in humans affected with diseases that are characterized in the generation of such aggregates.

  本发明涉及提供化合物、制备它们的方法以及它们在体内成像和量化β-淀粉样肽聚集物的使用。在本发明的一个优选方面，向人体注射示踪剂，并在含有淀粉样肽聚集物的身体部位显示富集。本发明的示踪剂可用于非侵入性地描绘和量化患有生成此类聚集物的疾病的人体内β-淀粉样肽聚集物。
• NOVEL COMPOUND HAVING AFFINITY FOR AMYLOID
  申请人：TANIFUJI Shigeyuki

  公开号：US20120271053A1

  公开（公告）日：2012-10-25

  The present invention provides a compound which has affinity with amyloid, shows sufficiently rapid clearance from normal tissues and is suppressed in toxicity such as mutagencity. Provided is a compound represented by the following formula (1) or a salt thereof: wherein A 1 , A 2 , A 3 and A 4 independently represents a carbon or nitrogen; R 1 is a halogen substituent; R 2 is a halogen substituent; and m is an integer of 0 to 2, provided that at least one of R 1 and R 2 is a radioactive halogen substituent, at least one of A 1 , A 2 , A 3 and A 4 represents a carbon, and R 1 binds to a carbon represented by A 1 , A 2 , A 3 or A 4 as well as a low-toxic diagnostic agent comprising a compound represented by the preceding formula or a salt thereof.

  本发明提供了一种与淀粉样物质亲和力较强、从正常组织中清除速度足够快且毒性如突变原性得到抑制的化合物。提供的化合物由以下公式（1）或其盐表示：其中，A1、A2、A3和A4独立地表示碳或氮；R1是卤素取代基；R2是卤素取代基；m是0到2的整数，但至少R1和R2中的一个是放射性卤素取代基，至少A1、A2、A3和A4中的一个表示碳，且R1结合到由A1、A2、A3或A4表示的碳，以及包含上述公式或其盐所表示的化合物的低毒性诊断剂。