The aims of this work were to develop (I) a brain-penetrant PDE4B-specific inhibitor for treatment of brain diseases to enhance the therapeutic efficacy while suppressing/avoiding gastrointestinal side effects which are suggested to be partially associated with inhibition of the PDE4D isoform, and (II) a PDE4B-selective radioligand for accurate target occupancy as well as enzyme density and biodistribution determinations by PET. The gene discussed is PDE4B; the disease is brain disorder.