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

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 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.

Язык: Английский

PET tracer development for imaging α-synucleinopathies

Archives of Pharmacal Research, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Язык: Английский

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

RSC Medicinal Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 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).

Язык: Английский