Synthesis of hypermodified adenosine derivatives as selective adenosine A3 receptor ligands.
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.
Cosyn
Liesbet
L
Laboratory for Medicinal Chemistry (FFW), UGent, Belgium.
Gao
Zhan-Guo
ZG
Van Rompaey
Philippe
P
Lu
Changrui
C
Jacobson
Kenneth A
KA
Van Calenbergh
Serge
S
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
D000588:Amines; D001386:Azides; D008024:Ligands; D043684:Receptor, Adenosine A3; D000241:Adenosine