title: Synthesis of hypermodified adenosine derivatives as selective adenosine A3 receptor ligands.
abstract: We investigated the A(3)AR affinity and selectivity of a series of 2-substituted 3'-azido and 3'-amino adenosine derivatives as well as some 5'-uronamide derivatives thereof. All compounds showed high A(3)AR selectivity. While the 3'-azides appeared to be A(3)AR antagonists with moderate A(3)AR affinity, their 3'-amino congeners exhibit significantly improved A(3)AR affinity and behave as partial agonists. For both the 3'-azides and the 3'-amines, the 5'-methylcarbamoyl modification improved the overall affinity. Introduction of a 2-phenylethynyl substituent provided high affinity for the A(3)AR.
authors.affiliation: Laboratory for Medicinal Chemistry (FFW), UGent, Belgium.
authors.forename: Liesbet
authors.initials: L
authors.lastname: Cosyn
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Gao
authors.forename: Philippe
authors.initials: P
authors.lastname: Van Rompaey
authors.forename: Changrui
authors.initials: C
authors.lastname: Lu
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D000588:Amines / Q000737:chemistry; D000818:Animals; D001386:Azides / Q000737:chemistry; D001665:Binding Sites; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D043684:Receptor, Adenosine A3 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000588:Amines; D001386:Azides; D008024:Ligands; D043684:Receptor, Adenosine A3; D000241:Adenosine