title: Allosteric modulators of the adenosine A1 receptor: synthesis and pharmacological evaluation of 4-substituted 2-amino-3-benzoylthiophenes.
abstract: A series of 4-substituted 2-amino-3-benzoylthiophenes was screened using a functional assay of A(1)AR-mediated phosphorylation of ERK1/2 in intact CHO cells to identify both potential agonistic effects as well the ability to allosterically modulate the activity of the orthosteric agonist, R-PIA. More detailed concentration-response experiments were subsequently performed on two compounds (9a and 9o) utilizing both the ERK1/2 assay as well as a second assay of [(35)S]GTPgammaS binding to activated G proteins.
authors.affiliation: Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurelio
authors.forename: Celine
authors.initials: C
authors.lastname: Valant
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Flynn
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sexton
authors.forename: Arthur
authors.initials: A
authors.lastname: Christopoulos
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scammells
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000494:Allosteric Regulation; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D013876:Thiophenes; C047235:N-(1-methyl-2-phenylethyl)adenosine; D048049:Extracellular Signal-Regulated MAP Kinases; D000241:Adenosine