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Discovery of a new human A2A adenosine receptor agonist, truncated 2-hexynyl-4′-thioadenosine

Title
Discovery of a new human A2A adenosine receptor agonist, truncated 2-hexynyl-4′-thioadenosine
Authors
Hou X.Kim H.O.Alexander V.Kim K.Choi S.Park S.-G.Lee J.H.Yoo L.S.Gao Z.-G.Jacobson K.A.Jeong L.S.
Ewha Authors
정낙신최선
SCOPUS Author ID
최선scopus
Issue Date
2010
Journal Title
ACS Medicinal Chemistry Letters
ISSN
1948-5875JCR Link
Citation
vol. 1, no. 9, pp. 516 - 520
Indexed
SCIE; SCOPUS WOS scopus
Abstract
The truncated C2- and C8-substituted 4′-thioadenosine derivatives 4a-d were synthesized from d-mannose, using palladium-catalyzed cross-coupling reactions as key steps. In this study, an A3 adenosine receptor (AR) antagonist, truncated 4′-thioadenosine derivative 3, was successfully converted into a potent A2A AR agonist 4a (Ki = 7.19 ± 0.6 nM) by appending a 2-hexynyl group at the C2-position of a derivative of 3 that was N6-substituted. However, C8-substitution greatly reduced binding affinity at the human A2A AR. All synthesized compounds 4a-d maintained their affinity at the human A3 AR, but 4a was found to be a competitive A3 AR antagonist/A2A AR agonist in cyclic AMP assays. This study indicates that the truncated C2-substituted 4′-thioadenosine derivatives 4a and 4b can serve as novel templates for the development of new A2A AR ligands. © 2010 American Chemical Society.
DOI
10.1021/ml1001823
Appears in Collections:
약학대학 > 약학과 > Journal papers
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