Novel Heterocyclic-Fused Pyridazinones as Potent and Selective Phosphodiesterase IV Inhibitors
Journal of Medicinal Chemistry1997Vol. 40(10), pp. 1417–1421
Citations Over TimeTop 15% of 1997 papers
Vittorio Dal Piaz, Maria Paola Giovannoni, Carla Castellana, José María Fernández Palacios, Jörge Beleta, Teresa Domènech, Vı́ctor Segarra
Abstract
A series of 6-aryl-4,5-heterocyclic-fused pyridazinones were designed and synthesized as selective phosphodiesterase (PDE) IV inhibitors. Biological evaluation of these compounds demonstrated a good selectivity profile toward the PDE IV family and greatly attenuated affinity for the Rolipram high-affinity binding site that seems to be responsible for undesiderable side effects. Structure-activity relationships (SARs) studies showed that the presence of an ethyl group at pyridazine N-2 is associated with the best potency and selectivity profile.
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