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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.
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页码:274 / 288
页数:15
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