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

Battistina Asproni; Gabriele Murineddu; Amedeo Pau; Gérard A Pinna; Morten Langgård; Claus Tornby Christoffersen; Jacob Nielsen; Jan Kehler

doi:10.1016/j.bmc.2010.10.038

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

Bioorg Med Chem. 2011 Jan 1;19(1):642-9. doi: 10.1016/j.bmc.2010.10.038. Epub 2010 Nov 17.

Authors

Battistina Asproni¹, Gabriele Murineddu, Amedeo Pau, Gérard A Pinna, Morten Langgård, Claus Tornby Christoffersen, Jacob Nielsen, Jan Kehler

Affiliation

¹ Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, Via F. Muroni 23/a, 07100 Sassari, Italy. asproni@uniss.it

PMID: 21087867
DOI: 10.1016/j.bmc.2010.10.038

Abstract

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 (IC(50)=16nM).

MeSH terms

Animals
Blood-Brain Barrier
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Mass Spectrometry
Mice
Models, Molecular
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

Substances

Phosphodiesterase Inhibitors
Quinazolines
Pde10a protein, mouse
Phosphoric Diester Hydrolases