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Synthesis and evaluation as PDE4 inhibitors of pyrimidine‐2,4‐dione derivatives
Author(s) -
Giovani Maria P.,
Graziano Alessia,
Matucci Rosanna,
Nesi Marta,
Cesari Nicoletta,
Vergelli Claudia,
Biancalani Claudio,
Crocetti Letizia,
Cilibrizzi Agostino,
Dal Piaz Vittorio
Publication year - 2011
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20395
Subject(s) - rolipram , chemistry , selectivity , pyrimidine , stereochemistry , phosphodiesterase 3 , phosphodiesterase , structure–activity relationship , enzyme , pharmacology , biochemistry , in vitro , biology , catalysis
A 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 (IC 50 = 5–14 µM) with a good selectivity toward PDE3 and PDE5. The same compounds demonstrate low affinity for the HARBS site with IC 50 values of 12–69 µM (IC 50 for Rolipram = 3.6 nM). Drug Dev Res 72: 274–288, 2011. © 2010 Wiley‐Liss, Inc.