Chalcone‐based derivatives as new scaffolds for hA3 adenosine receptor antagonists. (25th January 2013)

• Record Type: Journal Article
• Authors: Vazquez‐Rodriguez, Saleta; Matos, Maria João; Santana, Lourdes; Uriarte, Eugenio; Borges, Fernanda; Kachler, Sonja; Klotz, Karl‐Norbert
• Is Part Of: Journal of pharmacy and pharmacology. Volume 65:Number 5(2013:May)
• Page Start: 697
• Page End: 703
• Publication Date: 2013-01-25
• Subjects: Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12028
• Languages: English
• ISSNs: 0022-3573

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jphp12028-sec-0001" sec-type="section"> <title>Objectives</title> <p>With the aim of finding new adenosine receptor (AR) ligands based on the chalcone scaffold, we report the synthesis of a new series of coumarin–chalcone hybrids and the pharmacological characterization of their actions at four subtypes of AR.</p> </sec> <sec id="jphp12028-sec-0002" sec-type="section"> <title>Methods</title> <p>The synthesized compounds <bold>5</bold>–<bold>10</bold> were characterized in radioligand binding (A<sub>1</sub>, A<sub>2A</sub> and A<sub>3</sub>) and adenylyl cyclase activity assays (A<sub>2B</sub>) to determine the affinity of the compounds for the four human AR (<italic>h</italic>AR) subtypes.</p> </sec> <sec id="jphp12028-sec-0003" sec-type="section"> <title>Key findings</title> <p>Coumarin–chalcone hybrids were found to be ligands with a novel structure, not reported thus far, that showed varying affinity and selectivity for AR subtypes.</p> </sec> <sec id="jphp12028-sec-0004" sec-type="section"> <title>Conclusions</title> <p>The coumarin–chalcone hybrids in which ring B of the chalcone scaffold was a thiophene (compounds <bold>5</bold> and <bold>9</bold>) were found to be the most potent compounds of the series. Compound <bold>9</bold>, in which ring A of the chalcone moiety was the phenyl ring of the coumarin, showed similar activity against <italic>h</italic>A<sub>1</sub>, <italic>h</italic>A<sub>2A</sub> and <italic>h</italic>A<sub>3</sub> ARs, while compound <bold>5</bold>, in which ring A of the chalcone was substituted by the benzopyrone ring of the coumarin moiety, showed similar activity only at the <italic>h</italic>A<sub>3</sub> AR and, therefore, was deemed to be selective (K<sub>i</sub> (dissociation constant) = 5160 n<sc>m</sc>).</p> </sec> </abstract>