OBJECTIVES: 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. METHODS: The synthesized compounds 5-10 were characterized in radioligand binding (A1 , A2A and A3 ) and adenylyl cyclase activity assays (A2B ) to determine the affinity of the compounds for the four human AR (hAR) subtypes. KEY FINDINGS: 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. CONCLUSIONS: The coumarin-chalcone hybrids in which ring B of the chalcone scaffold was a thiophene (compounds 5 and 9) were found to be the most potent compounds of the series. Compound 9, in which ring A of the chalcone moiety was the phenyl ring of the coumarin, showed similar activity against hA1 , hA2A and hA3 ARs, while compound 5, in which ring A of the chalcone was substituted by the benzopyrone ring of the coumarin moiety, showed similar activity only at the hA3 AR and, therefore, was deemed to be selective (Ki (dissociation constant) = 5160 nm).
OBJECTIVES: 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. METHODS: The synthesized compounds 5-10 were characterized in radioligand binding (A1 , A2A and A3 ) and adenylyl cyclase activity assays (A2B ) to determine the affinity of the compounds for the four humanAR (hAR) subtypes. KEY FINDINGS: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. CONCLUSIONS: The coumarin-chalcone hybrids in which ring B of the chalcone scaffold was a thiophene (compounds 5 and 9) were found to be the most potent compounds of the series. Compound 9, in which ring A of the chalcone moiety was the phenyl ring of the coumarin, showed similar activity against hA1 , hA2A and hA3 ARs, while compound 5, in which ring A of the chalcone was substituted by the benzopyrone ring of the coumarin moiety, showed similar activity only at the hA3AR and, therefore, was deemed to be selective (Ki (dissociation constant) = 5160 nm).
Authors: Lígia R Gomes; John Nicolson Low; André Fonseca; Maria João Matos; Fernanda Borges Journal: Acta Crystallogr E Crystallogr Commun Date: 2016-06-10