Synthesis and SAR study of new phenylimidazole-pyrazolo[1,5-c]quinazolines as potent phosphodiesterase 10A inhibitors

Synthesis, inhibition of PDE10A activity of new phenylimidazole-pyrazolo[1,5-c]quinazolines (1) are described. A series of phenylimidazole-pyrazolo[1,5-c]quinazolines 1a–q was designed, synthesized and characterised as a novel class of potent phophodiesterase 10A (PDE10A) inhibitors. In this series,...

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Veröffentlicht in:	Bioorganic & medicinal chemistry 2011-01, Vol.19 (1), p.642-649
Hauptverfasser:	Asproni, Battistina, Murineddu, Gabriele, Pau, Amedeo, Pinna, Gérard A., Langgård, Morten, Christoffersen, Claus Tornby, Nielsen, Jacob, Kehler, Jan
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Blood-Brain Barrier enzyme inhibitors esterases imidazoles Inhibitory Concentration 50 Magnetic Resonance Spectroscopy Mass Spectrometry Mice Models, Molecular PDE10A inhibition Phenylimidazole-pyrazolo[1,5-c]quinazolines Phosphodiesterase Inhibitors - chemical synthesis Phosphodiesterase Inhibitors - chemistry Phosphodiesterase Inhibitors - pharmacology Phosphoric Diester Hydrolases - drug effects Quinazolines - chemical synthesis Quinazolines - chemistry Quinazolines - pharmacology Structure-Activity Relationship Structure–activity relationships synthesis
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Zusammenfassung:	Synthesis, inhibition of PDE10A activity of new phenylimidazole-pyrazolo[1,5-c]quinazolines (1) are described. A series of phenylimidazole-pyrazolo[1,5-c]quinazolines 1a–q was designed, synthesized and characterised as a novel class of potent phophodiesterase 10A (PDE10A) inhibitors. In this series, 2,9-dimethyl-5-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethyl)pyrazolo[1,5-c]quinazoline (1q) showed the highest affinity for PDE10A enzyme (IC50=16nM).
ISSN:	0968-0896 1464-3391
DOI:	10.1016/j.bmc.2010.10.038