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Structure-Activity Relationships of Radioiodinated 6,5,6-Tricyclic Compounds for the Development of Tau Imaging Probes.

ABSTRACT: Tau aggregate, which is the main component of the neurofibrillary tangle, is an attractive imaging target for diagnosing and monitoring the progression of Alzheimer's disease (AD). In this study, we designed and synthesized six radioiodinated 6,5,6-tricyclic compounds to explore novel scaffolds for tau imaging probes. On in vitro autoradiography of AD brain sections, pyridoimidazopyridine and benzimidazopyrimidine derivatives ([¹²⁵I]21 and [¹²⁵I]22, respectively) showed selective binding affinity for tau aggregates, whereas carbazole, pyrrolodipyridine, and pyridoimidazopyrimidine derivatives ([¹²⁵I]10, [¹²⁵I]12, and [¹²⁵I]23, respectively) bound ?-amyloid aggregates. In a biodistribution study using normal mice, [¹²⁵I]21 and [¹²⁵I]22 showed high initial uptakes (5.73 and 5.66% ID/g, respectively, at 2 min postinjection) into and rapid washout (0.14 and 0.10% ID/g, respectively, at 60 min postinjection) from the brain. Taken together, two novel scaffolds including pyridoimidazopyridine and benzimidazopyrimidine may be applied to develop useful tau imaging probes.

SUBMITTER: Watanabe H

PROVIDER: S-EPMC7025389 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Structure-Activity Relationships of Radioiodinated 6,5,6-Tricyclic Compounds for the Development of Tau Imaging Probes.

Watanabe Hiroyuki H Tatsumi Haruka H Kaide Sho S Shimizu Yoichi Y Iikuni Shimpei S Ono Masahiro M

ACS medicinal chemistry letters 20200109 2

Tau aggregate, which is the main component of the neurofibrillary tangle, is an attractive imaging target for diagnosing and monitoring the progression of Alzheimer's disease (AD). In this study, we designed and synthesized six radioiodinated 6,5,6-tricyclic compounds to explore novel scaffolds for tau imaging probes. On in vitro autoradiography of AD brain sections, pyridoimidazopyridine and benzimidazopyrimidine derivatives ([125I]21 and [125I]22, res ...[more]

PMID: 32071677

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Dataset Information

Structure-Activity Relationships of Radioiodinated 6,5,6-Tricyclic Compounds for the Development of Tau Imaging Probes.

Publications

Structure-Activity Relationships of Radioiodinated 6,5,6-Tricyclic Compounds for the Development of Tau Imaging Probes.

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