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

来源：

DRUG DEVELOPMENT RESEARCH | 2011年 / 72卷 / 03期

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

页码：274 / 288

页数：15

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