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Conversion of A3 adenosine receptor agonists into selective antagonists by modification of the 5′-ribofuran-uronamide moiety

Title
Conversion of A3 adenosine receptor agonists into selective antagonists by modification of the 5′-ribofuran-uronamide moiety
Authors
Gao Z.-G.Joshi B.V.Klutz A.M.Kim S.-K.Lee H.W.Kim H.O.Jeong L.S.Jacobson K.A.
Ewha Authors
정낙신
Issue Date
2006
Journal Title
Bioorganic and Medicinal Chemistry Letters
ISSN
0960-894XJCR Link
Citation
Bioorganic and Medicinal Chemistry Letters vol. 16, no. 3, pp. 596 - 601
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
The highly selective agonists of the A3 adenosine receptor (AR), Cl-IB-MECA (2-chloro-N6-(3-iodobenzyl)-5′-N- methylcarboxamidoadenosine), and its 4′-thio analogue, were successfully converted into selective antagonists simply by appending a second N-methyl group on the 5′-uronamide position. The 2-chloro-5′-(N,N-dimethyl) uronamido analogues bound to, but did not activate, the human A3AR, with Ki values of 29 nM (4′-O) and 15 nM (4′-S), showing >100-fold selectivity over A1, A2A, and A 2BARs. Competitive antagonism was demonstrated by Schild analysis. The 2-(dimethylamino)-5′-(N,N-dimethyl)uronamido substitution also retained A3AR selectivity but lowered affinity. © 2005 Elsevier Ltd. All rights reserved.
DOI
10.1016/j.bmcl.2005.10.054
Appears in Collections:
약학대학 > 약학과 > Journal papers
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