title: 5-Substituted 2-aminothiophenes as A1 adenosine receptor allosteric enhancers.
abstract: Two series of 5-substituted 2-amino-4-(3-trifluoromethylphenyl)thiophenes were prepared and evaluated as allosteric enhancers at the A(1) adenosine receptor (A(1)AR). In the 3-benzoyl series, a 5-phenyl group was found to confer the greatest potency (9a: ED(50)=2.1 microM, AE score=18%). However, the analogue with no 5-substituent (6b: ED(50)=15.8 microM, AE score=77%) proved to be the most efficacious. In the 3-ethoxycarbonyl series, the 5-(4-chlorophenyl) analogue was clearly the most potent and efficacious (9l: ED(50)=6.6 microM, AE score=57%). The antagonist activity of all compounds was measured using a [(3)H]CPX competitive binding assay.
authors.affiliation: Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville VIC 3052, Australia.
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurelio
authors.forename: Heidi
authors.initials: H
authors.lastname: Figler
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Flynn
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scammells
mesh_terms: D058916:Adenosine A1 Receptor Antagonists; D000494:Allosteric Regulation; D000586:Amination; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D015394:Molecular Structure; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D000814:Aniline Compounds; D002264:Carboxylic Acids; D043682:Receptor, Adenosine A1; C005464:2-aminothiophenol