title: Exploring human adenosine A3 receptor complementarity and activity for adenosine analogues modified in the ribose and purine moiety.
abstract: In this paper we investigated the influence on affinity, selectivity and intrinsic activity upon modification of the adenosine agonist scaffold at the 3'- and 5'-positions of the ribofuranosyl moiety and the 2- and N6-positions of the purine base. This resulted in the synthesis of various analogues, that is, 3-12 and 24-33, with good hA3AR selectivity and moderate-to-high affinities (as in 32, Ki=27 nM). Interesting was the ability to tune the intrinsic activity depending on the substituent introduced at the 3'-position.
authors.affiliation: Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Van Rompaey
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Ariel S
authors.initials: AS
authors.lastname: Gross
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Gao
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011687:Purines / Q000737:chemistry*; D051381:Rats; D043684:Receptor, Adenosine A3 / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012266:Ribose / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D011687:Purines; D043684:Receptor, Adenosine A3; D011994:Recombinant Proteins; D012266:Ribose; D000242:Cyclic AMP; D000241:Adenosine