ABSTRACT
4'-Thionucleoside derivatives as potent and selective A3 adenosaine receptor agonists were synthesized, starting from D-gulono-gamma-lactone via D-thioribosyl acetate as a key intermediate, among which the 2-chloro-N6-methyladenosine-5-methyluronamide showed the most potent and selective binding affinity (Ki = 0.28 +/- 0.09 nM) at the human A3 adenosine receptor.
Subject(s)
Adenosine A3 Receptor Agonists , Adenosine/analogs & derivatives , Receptor, Adenosine A3/chemistry , Thionucleosides/chemistry , Acetates/chemistry , Adenosine/chemistry , Animals , Furans/chemistry , Gluconates/chemistry , Humans , Kinetics , Lactones/chemistry , Ligands , Models, Chemical , Nucleosides/chemistry , Oxygen/chemistry , Protein Binding , RatsABSTRACT
Novel 3'-ureidoadenosine analogues were synthesized from 1,2:5, 6-di-O-isopropylidene-D-glucose in order to lead to stronger hydrogen bonding at the A3 adenosine receptor than the corresponding 3'-aminoadenosine derivatives. However, all synthesized 3'-ureidoadenosine analogues have lost their binding affinities to the all subtypes of adenosine receptors, indicating that bulky 3'-urea moiety led to conformational distortion.