2-(4-methoxyphenyl)-6-iodoimidazo[1,2-a]pyridine | 477871-43-5

• 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-methoxyphenyl)-6-iodoimidazo[1,2-a]pyridine
• 英文别名: 6-iodo-2-(4 - methoxyphenyl)imidazo[1,2-a]pyridine；6-Iodo-2-(4-methoxyphenyl)imidazo[1,2-a]pyridine
• CAS: 477871-43-5
• 化学式: C₁₄H₁₁IN₂O
• 分子量: 350.159
• InChiKey: AYUXAGCPNOTWDR-UHFFFAOYSA-N

物化性质

• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  26.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-methoxyphenyl)-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41.2%的产率得到2-(4′-methoxyphenyl)-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 以 1,4-二氧六环 、 甲醇 、 正己烷 、 乙腈 为溶剂， 反应 29.5h， 生成 2-(4-methoxyphenyl)-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。
• NOVEL COMPOUND WITH AFFINITY FOR AMYLOID
  申请人：Tanifuji Shigeyuki

  公开号：US20090252680A1

  公开（公告）日：2009-10-08

  A compound represented by the following formula or a salt thereof: wherein each of A 1 , A 2 , A 3 and A 4 independently represents a carbon or nitrogen; R 1 is a group selected from the group consisting of hydrogen, hydroxyl group, carboxyl group, sulfuric acid group, amino group, nitro group, cyano group, non-radioactive halogen substituents, alkyl substituents with 1-4 carbon atoms and alkoxy substituents with 1-4 carbon atoms; and R 2 is a radioactive halogen substituent, provided at least one of A 1 , A 2 , A 3 and A 4 represents a carbon, and R1 binds to a carbon represented by A 1 , A 2 , A 3 or A 4 , is effective as an image diagnosis probe targeting amyloid and as well as a diagnostic agent for Alzheimer's disease including the compound represented by the above formula or a salt thereof.

  以下化合物或其盐所代表的化合物： 其中A1，A2，A3和A4各自独立地代表碳或氮；R1是从氢，羟基，羧基，硫酸基，氨基，硝基，氰基，非放射性卤素取代基，1-4个碳原子的烷基取代基和1-4个碳原子的烷氧基取代基的群中选择的基团；而R2是放射性卤素取代基，前提是A1，A2，A3和A4中至少有一个代表碳，并且R1与A1，A2，A3或A4代表的碳结合，该化合物或其盐的有效成分作为靶向淀粉样蛋白的影像诊断探针以及阿尔茨海默病的诊断剂。
• USE OF NOVEL COMPOUND HAVING AFFINITY FOR AMYLOID, AND PROCESS FOR PRODUCTION OF THE SAME
  申请人：Tanifuji Shigeyuki

  公开号：US20100216994A1

  公开（公告）日：2010-08-26

  The invention provides a reagent which can detect amyloid in vitro and in vivo with high sensitivity using a compound which has affinity with amyloid. The reagent for detecting amyloid deposited in a biological tissue comprises the compound represented by the following formula (1) or a salt thereof: wherein A 1 , A 2 , A 3 and A 4 independently represent a carbon or nitrogen, R 2 is a group selected from the group consisting of a hydrogen, hydroxyl group, carboxyl group, sulfuric acid group, amino group, nitro group, cyano group, non-radioactive halogen substituent, alkyl substituent with 1 to 4 carbon atoms and alkoxy substituent with 1 to 4 carbon atoms, and R 2 is a radioactive halogen substituent, provided that 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 .

  本发明提供了一种试剂，可使用与淀粉样物具有亲和性的化合物，在体内外高灵敏度地检测淀粉样物。用于检测生物组织中沉积的淀粉样物的试剂包括下式（1）所表示的化合物或其盐：其中，A1、A2、A3和A4独立地表示碳或氮，R2是从氢、羟基、羧基、硫酸基、氨基、硝基、氰基、非放射性卤素取代基、具有1至4个碳原子的烷基取代基和具有1至4个碳原子的烷氧基取代基组成的群中选择的一种基团，且R2是放射性卤素取代基，但至少A1、A2、A3和A4中的一个表示碳，并且R1结合到由A1、A2、A3或A4表示的碳。
• NOVEL COMPOUNDS WITH AFFINITY FOR AMYLOID
  申请人：NIHON MEDI-PHYSICS CO., LTD.

  公开号：EP2098523A1

  公开（公告）日：2009-09-09

  It is intended to provide a compound effective as an image diagnosis probe targeting amyloid and a diagnostic agent for Alzheimer's disease comprising the compound. Provided is a compound represented by the following formula or a salt thereof: wherein A1, A2, A3 and A4 independently represents a carbon or nitrogen, R1 is a group selected from the group consisting of hydrogen, hydroxyl group, carboxyl group, sulfuric acid group, amino group, nitro group, cyano group, non-radioactive halogen substituents, alkyl substituents with 1-4 carbon atoms and alkoxy substituents with 1-4 carbon atoms, and R3 is a radioactive halogen substituent, provided that at least one of A1 A2, A3 and A4 represents a carbon, and R1 binds to a carbon represented by A1, A2, A3 or A4, as well as a diagnostic agent for Alzheimer's disease comprising the compound represented by the above formula or a salt thereof.

  本发明旨在提供一种作为针对淀粉样蛋白的图像诊断探针有效的化合物，以及一种包含该化合物的阿尔茨海默病诊断剂。本发明提供了由下式代表的化合物或其盐： 其中 A1、A2、A3 和 A4 独立地代表碳或氮、 R1 是选自由氢、羟基、羧基、硫酸基、氨基、硝基、氰基、非放射性卤素取代基、1-4 个碳原子的烷基取代基和 1-4 个碳原子的烷氧基取代基组成的基团，以及 R3 是放射性卤素取代基、 条件是 A1 A2、A3 和 A4 中至少有一个代表碳，且 R1 与 A1、A2、A3 或 A4 所代表的碳结合，以及由上式所代表的化合物或其盐组成的阿尔茨海默病诊断剂。
• EP2098523
  申请人：——

  公开号：——

  公开（公告）日：——