title: Synthesis and SAR study of new phenylimidazole-pyrazolo[1,5-c]quinazolines as potent phosphodiesterase 10A inhibitors.
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).
authors.affiliation: Dipartimento Farmaco Chimico Tossicologico, Università di Sassari, Via F. Muroni 23/a, 07100 Sassari, Italy. asproni@uniss.it
authors.forename: Battistina
authors.initials: B
authors.lastname: Asproni
authors.forename: Gabriele
authors.initials: G
authors.lastname: Murineddu
authors.forename: Amedeo
authors.initials: A
authors.lastname: Pau
authors.forename: Gérard A
authors.initials: GA
authors.lastname: Pinna
authors.forename: Morten
authors.initials: M
authors.lastname: Langgård
authors.forename: Claus Tornby
authors.initials: CT
authors.lastname: Christoffersen
authors.forename: Jacob
authors.initials: J
authors.lastname: Nielsen
authors.forename: Jan
authors.initials: J
authors.lastname: Kehler
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008958:Models, Molecular; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010726:Phosphodiesterase Inhibitors; D011799:Quinazolines; C492284:Pde10a protein, mouse; D010727:Phosphoric Diester Hydrolases