1383554-74-2Relevant articles and documents
Truncated nucleosides as A3 adenosine receptor ligands: Combined 2-arylethynyl and bicyclohexane substitutions
Tosh, Dilip K.,Paoletta, Silvia,Phan, Khai,Gao, Zhan-Guo,Jacobson, Kenneth A.
, p. 596 - 601 (2012/10/18)
C2-Arylethynyladenosine-5′-N-methyluronamides containing a bicyclo[3.1.0]hexane [(N)-methanocarba] ring are selective A3 adenosine receptor (AR) agonists. Similar 4′-truncated C2-arylethynyl-(N)-methanocarba nucleosides containing alkyl or alkylaryl groups at the N6 position were low-efficacy agonists or antagonists of the human A3AR with high selectivity. Higher hA3AR affinity was associated with N6-methyl and ethyl (Ki = 3-6 nM) than with N6-arylalkyl groups. However, combined C2-phenylethynyl and N6-2-phenylethyl substitutions in selective antagonist 15 provided a Ki of 20 nM. Differences between 4′-truncated and nontruncated analogues of extended C2-p-biphenylethynyl substitution suggested a ligand reorientation in AR binding, dominated by bulky N6 groups in analogues lacking a stabilizing 5′-uronamide moiety. Thus, 4′-truncation of C2-arylethynyl-(N)-methanocarba adenosine derivatives is compatible with general preservation of A3AR selectivity, especially with small N6 groups, but reduced efficacy in A3AR-induced inhibition of adenylate cyclase. This article not subject to U.S. Copyright. Published 2012 by the American Chemical Society.
