Exploring human adenosine A3 receptor complementarity and activity for adenosine analogues modified in the ribose and purine moiety.
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.
Van Rompaey
Philippe
P
Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.
Jacobson
Kenneth A
KA
Gross
Ariel S
AS
Gao
Zhan-Guo
ZG
Van Calenbergh
Serge
S
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
D011687:Purines; D043684:Receptor, Adenosine A3; D011994:Recombinant Proteins; D012266:Ribose; D000242:Cyclic AMP; D000241:Adenosine