New irreversible adenosine A(1) antagonists based on FSCPX.
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.
Beauglehole
Anthony R
AR
Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Baker
Stephen P
SP
Scammells
Peter J
PJ
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
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