N-Arylrolipram derivatives as potent and selective PDE4 inhibitors

Derivatization of rolipram led to the identification of 3-[4-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxo-pyrrolidin-1-yl]-5-(3-methoxybenzyloxy)-benzoic acid N′, N′-dimethylhydrazide ( 4 ), a potent and selective inhibitor of PDE4, which inhibits the activation of human leukocytes with pIC 50 values in the range of 7.3 – 7.8, and blocks antigen induced eosinophilia in Brown Norway rats at a dose of 1 mg/kg (i.t.). A rolipram derivative was identified which is a potent and selective inhibitor of PDE4 and shows promising activity in cellular assay and in vivo models.