New irreversible adenosine A1 antagonists based on FSCPX

FSCPX (1) and its amide analogue (2) have been reported to exhibit potent and selective irreversible antagonism of the A1 adenosine receptor (A1AR) when used in in vitro biological preparations. In order to obtain an irreversible A1AR 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 A1AR and concentration-dependent irreversible binding to the A1AR.