Synthesis and biological activity of pyrido[3',2':4,5]furo[3,2-d]pyrimidine derivatives as novel and potent phosphodiesterase type 4 inhibitors.
Taltavull J, Serrat J, Gràcia J, Gavaldà A, Córdoba M, Calama E, Montero JL, Andrés M, Miralpeix M, Vilella D, Hernández B, Beleta J, Ryder H, Pagès L.
A series of pyrido[3',2':4,5]furo[3,2-d]pyrimidines (PFP) were synthesized and tested for phosphodiesterase type 4 (PDE4) inhibitory activity, with the potential to treat asthma and chronic obstructive pulmonary disease (COPD). Structure-activity relationships within this series, leading to an increase of potency on the enzyme, is presented. Both gem-dimethylcyclohexyl moieties fused to the pyridine ring and the substitution at the 5 position of the PFP scaffold, proved to be key elements in order to get a high affinity in the enzyme.