New chromene scaffolds for adenosine A(2A) receptors: synthesis, pharmacology and structure-activity relationships.

In silico screening of a collection 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. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Citation

Filipe Areias, Marta Costa, Marián Castro, José Brea, Elisabet Gregori-Puigjané, M Fernanda Proença, Jordi Mestres, María I Loza. New chromene scaffolds for adenosine A(2A) receptors: synthesis, pharmacology and structure-activity relationships. European journal of medicinal chemistry. 2012 Aug;54:303-10

Mesh Tags

Substances

PMID: 22677030

search → result