Synthesis and Evaluation as PDE4 Inhibitors of Pyrimidine-2,4-dione Derivatives

被引:3
|
作者
Giovannoni, Maria P. [1 ]
Graziano, Alessia [1 ]
Matucci, Rosanna [2 ]
Nesi, Marta [2 ]
Cesari, Nicoletta [1 ]
Vergelli, Claudia [1 ]
Biancalani, Claudio [1 ]
Crocetti, Letizia [1 ]
Cilibrizzi, Agostino [1 ]
Dal Piaz, Vittorio [1 ]
机构
[1] Dipartimento Sci Farmaceut, I-50019 Florence, Italy
[2] Dipartimento Farmacol Preclin & Clin MA Mancini, Florence, Italy
关键词
HARBS; PDE4; selectivity; CROSS-COUPLING REACTIONS; PHOSPHODIESTERASE-4; INHIBITORS; C-N; POTENT; ROLIPRAM; BINDING; SUPPRESSION; THALIDOMIDE; EXPRESSION; ANALOGS;
D O I
10.1002/ddr.20395
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 (IC50 = 5-14 mu M) with a good selectivity toward PDE3 and PDE5. The same compounds demonstrate low affinity for the HARBS site with IC50 values of 12-69 mu M (IC50 for Rolipram = 3.6 nM). Drug Dev Res 72:274-288, 2011. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:274 / 288
页数:15
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