Synthesis and evaluation as PDE4 inhibitors of pyrimidine‐2,4‐dione derivatives

Abstract

AbstractA series of nitraquazone analogs with a pyrimidindione core was synthesized and tested for inhibitory activity on PDE4, selectivity versus PDE3 and PDE5 and for affinity towards the rolipram high‐affinity binding site (HARBS). The 5‐anilino derivatives 13–18 showed the best profile combining appreciable PDE4 inhibitory activity (IC50 = 5–14 µM) with a good selectivity toward PDE3 and PDE5. The same compounds demonstrate low affinity for the HARBS site with IC50 values of 12–69 µM (IC50 for Rolipram = 3.6 nM). Drug Dev Res 72: 274–288, 2011. © 2010 Wiley‐Liss, Inc.