title: New irreversible adenosine A(1) antagonists based on FSCPX.
abstract: FSCPX (1) and its amide analogue (2) have been reported to exhibit potent and selective irreversible antagonism of the A(1) adenosine receptor (A(1)AR) when used in in vitro biological preparations. In order to obtain an irreversible A(1)AR antagonist with improved stability, analogues of FSCPX incorporating the chemoreactive 4-(fluorosulfonyl)phenyl moiety separated from the xanthine pharmacophore by a ketone linkage were explored. Compounds 4a-c exhibited improved affinity for the A(1)AR and concentration-dependent irreversible binding to the A(1)AR.
authors.affiliation: Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Beauglehole
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Baker
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scammells
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007202:Indicators and Reagents; D058915:Purinergic P1 Receptor Antagonists; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D007202:Indicators and Reagents; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C100640:8-cyclopentyl-3-(3-((4-(fluorosulfonyl)benzoyl)oxy)propyl)-1-propylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine