期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 54, 期 -, 页码 303-310出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2012.05.009
关键词
G protein-coupled receptors; Structure-activity relationship; Adenosine receptors; Knoevenagel condensation; Chromene scaffolds
资金
- Spanish Ministerio de Ciencia e Innovacion [HF2007-0055, BIO2008-02329]
- Portuguese Fundacao para a Ciencia e Tecnologia [PPCDT/QUI/59356/2004]
- Xunta de Galicia [07CSA003203PR, 08CSA020203PR]
- Instituto de Salud Carlos III
- Isabel Barreto Contract from the Xunta de Galicia
- Portuguese FCT [SFRH/BPD/79609/2011, SFRH/BPD/26106/2005]
- Fundação para a Ciência e a Tecnologia [SFRH/BPD/26106/2005] Funding Source: FCT
In silico screening of a c ollection of 1584 academic compounds identified a small molecule hit for the human adenosine A(2A) receptor (pK(i) = 6.2) containing a novel chromene scaffold (3a). To explore the structure activity relationships of this new chemical series for adenosine receptors, a focused library of 43 2H-chromene-3-carboxamide derivatives was synthesized and tested in radioligand binding assays at human adenosine A(1), A(2A), A(2B) and A(3) receptors. The series was found to be enriched with bioactive compounds for adenosine receptors, with 14 molecules showing submicromolar affinity (pK(i) >= 6.0) for at least one adenosine receptor subtype. These results provide evidence that the chromene scaffold, a core structure present in natural products from a wide variety of plants, vegetables, and fruits, constitutes a valuable source for novel therapeutic agents. (C) 2012 Elsevier Masson SAS. All rights reserved.
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