Details

Autor(en) / Beteiligte

• Liu, Jianrong
• Maisonial-Besset, Aurélie
• Wenzel, Barbara
• Canitrot, Damien
• Baufond, Ariane
• Chezal, Jean-Michel
• Brust, Peter
• Moreau, Emmanuel

Titel

Synthesis and in vitro evaluation of new fluorinated quinoline derivatives with high affinity for PDE5: Towards the development of new PET neuroimaging probes

Ist Teil von

• European journal of medicinal chemistry, 2017-08, Vol.136, p.548-560

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The increasing incidence of Alzheimer's disease (AD) worldwide is a major public health problem. Current treatments provide only palliative solutions with significant side effects. Therefore, new efficient treatment options and novel early diagnosis tools are urgently needed. Recently, strong pre-clinical evidences suggested that phosphodiesterase 5 (PDE5) may be clinically relevant both as biomarker and drug-target in AD. In this study, we intended to develop a new radiofluorinated tracer for the visualisation of PDE5 in brain using PET imaging. Based on currently known PDE5 inhibitors, a series of novel fluorinated compounds bearing a quinoline core have been synthesised via multi-steps reaction pathways. Their affinity for PDE5 and selectivity over other PDE families have been investigated. According to the data collected from this in vitro screening, fluorinated derivatives 24a, b bearing a fluoroethoxy group at the C-3 position of the quinoline core appeared to be the most promising structures and will be further radiolabelled with fluorine-18 for in vitro and in vivo evaluations as PET radiotracer for neuroimaging of PDE5. [Display omitted] •New fluorinated inhibitors of the PDE5 enzyme were synthesised and evaluated in vitro.•Small fluoro-containing alkyl side chains did not alter the inhibitory potency.•Compounds 24a, b appeared to be most promising regarding affinity and selectivity.•Compounds 24a, b were selected for radiolabelling with fluorine-18 and PET imaging.