RESUMEN
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.
Asunto(s)
Agonistas del Receptor de Adenosina A3 , Adenosina/análogos & derivados , Receptor de Adenosina A3/química , Tionucleósidos/química , Acetatos/química , Adenosina/química , Animales , Furanos/química , Gluconatos/química , Humanos , Cinética , Lactonas/química , Ligandos , Modelos Químicos , Nucleósidos/química , Oxígeno/química , Unión Proteica , RatasRESUMEN
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.