Structure–Activity Relationships and Evaluation of 2-(Heteroaryl-cycloalkyl)-1H-indoles as Tauopathy Positron Emission Tomography Radiotracers

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Structure–activity relationship studies were performed on a library of synthesized compounds based previously identified tau ligands. The top 13 new had Ki values in the range 5–14 nM Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) post-mortem brain tissues. One more promising ([3H]75) bound with high affinity AD, PSP, CBD tissues (KD's = 1–1.5 nM) Pick's tissue (KD 3.8 nM). Autoradiography [3H]75 demonstrated specific binding Nonhuman primate PET imaging [18F]75 peak standardized uptake value (SUV) ∼5 cerebellum, ∼4.5 cortex, ∼4 whole SUV 2-to-90 min ratios 3.9 brain, 4.9 4.5 cerebellum. Compound is candidate for translation to human studies.

Language: Английский

PET tracer development for imaging α-synucleinopathies

Archives of Pharmacal Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

Strategies of Positron Emission Tomography (PET) tracer development for imaging of Tau and α-Synuclein in neurodegenerative disorders

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Advances in the positron emission tomography (PET) tracer development for imaging of tau Alzheimer's disease (AD) and non-AD, α-synuclein Parkinson's (PD).

Language: Английский