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Coumarins and adenosine receptors: New perceptions in structure–affinity relationships
Author(s) -
Fonseca André,
Matos Maria João,
Vilar Santiago,
Kachler Sonja,
Klotz KarlNorbert,
Uriarte Eugenio,
Borges Fernanda
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13075
Subject(s) - adenylyl cyclase , receptor , context (archaeology) , chemistry , adenosine receptor , coumarin , radioligand , adenosine , g protein coupled receptor , biochemistry , pharmacology , stereochemistry , computational biology , biology , agonist , paleontology , organic chemistry
Adenosine receptor ( AR ) subtypes are involved in several physiological and pharmacological processes. Ligands that are able to selectively modulate one receptor subtype can delay or slow down the progression of diverse diseases. In this context, our research group focused its investigation into the discovery and development of novel, potent and selective AR ligands based on coumarin scaffold. Therefore, a series of 3‐phenylcarboxamidocoumarins were synthesized and their affinity for the human AR subtypes was screened by radioligand binding assays for A 1 , A 2A and A 3 receptors and for A 2B by adenylyl cyclase assay. Compound 26 was found to be the most remarkable, with a h A 1 / h A 3 and h A 2A / h A 3 selectivity of 42, for the A 3 AR ( K i = 2.4 μ m ). Receptor‐driven molecular modelling studies have provided valuable information on the binding/selectivity data of compound 26 and for the following optimization process. Moreover, compound 26 presents drug‐like properties according to the general guidelines linked to the concept.