NOVEL HETEROCYCLIC-FUSED PYRIDAZINONES AS POTENT AND SELECTIVE PHOSPHODIESTERASE-IV INHIBITORS

A series of 6-aryl-4,5-heterocyclic-fused pyridazinones were designed and synthesized as selective phosphodiesterase (PDE) TV inhibitors. Bi ological evaluation of these compounds demonstrated a good selectivity profile toward the PDE TV family and greatly attenuated affinity for the Rolipram high-affinity binding site that seems to be responsible f or 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.