title: Ligands and therapeutic perspectives of adenosine A(2A) receptors.
abstract: Adenosine A(2A) receptors are members of the G protein-coupled receptor family and mediate multiple physiological effects of adenosine, both at the central nervous system (CNS) and at peripheral tissues, by activating several pathways or interacting with other receptors or proteins. Increasing evidence relate A(2A) receptors with pharmacological stress testing, neurodegenerative disorders (such as Parkinson's disease) and inflammation, renewing the interest in these receptors, increasingly viewed as promising therapeutic targets. Series of agonists and antagonists have been developed by medicinal chemistry artwork either by structure activity relationship (SAR) or quantitative structure activity relationship (QSAR) studies. These studies have allowed identification of the structural and electrostatic requirements for high affinity A(2A) receptor binding and, therefore, contributing to the rational design of A(2A) receptor ligands. Additional rational chemical modifications of the existing A(2A) receptor ligands may further improve their affinity/selectivity. The purpose of this review is to analize and summarize aspects related to the medicinal chemistry of A(2A) receptor ligands, their present and potencial therapeutic applications by exploring the molecular structure and physiological and pathophysiological roles of A(2A) receptors.
authors.affiliation: Serviço de Farmacologia, REQUIMTE/FARMA, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Diniz
authors.forename: F
authors.initials: F
authors.lastname: Borges
authors.forename: L
authors.initials: L
authors.lastname: Santana
authors.forename: E
authors.initials: E
authors.lastname: Uriarte
authors.forename: J M A
authors.initials: JM
authors.lastname: Oliveira
authors.forename: J
authors.initials: J
authors.lastname: Gonçalves
authors.forename: P
authors.initials: P
authors.lastname: Fresco
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D043705:Receptor, Adenosine A2A / Q000502:physiology; D019820:Xanthine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D019086:Bridged Bicyclo Compounds, Heterocyclic; D008024:Ligands; D009705:Nucleosides; D043705:Receptor, Adenosine A2A; D019820:Xanthine