| Autor: |
Kenneth A. Jacobson, Lak Shin Jeong, Lena S. Yoo, Zhan Guo Gao, Jin Hee Lee, Hea Ok Kim, Xiyan Hou, Seul Gi Park, Sun Choi, Kyunglim Kim, Varughese Alexander |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
ACS Medicinal Chemistry Letters. 1:516-520 |
| ISSN: |
1948-5875 |
| DOI: |
10.1021/ml1001823 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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