Synthesis and Biological Activity of a New Series of N6-Arylcarbamoyl, 2-(Ar)alkynyl-N6-arylcarbamoyl, and N6-Carboxamido Derivatives of Adenosine-5‘-N-ethyluronamide as A1 and A3 Adenosine Receptor Agonists
| Autor: | Barbara Cacciari, G. Cristalli, G. Spalluto, Xiao-duo Ji, Pineda de Las Infantas Mj, Volpini R, R. Romagnoli, Kenneth A. Jacobson, Neli Melman, Stefano Costanzi, S. Vittori, Park Ks, Pier Giovanni Baraldi |
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| Rok vydání: | 1998 |
| Předmět: | |
| Zdroj: | Journal of Medicinal Chemistry. 41:3174-3185 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm980147p |
| Popis: | A new series of 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-β-d-ribofuranuronamide-bearing N-arylureas or N-arylcarboxamido groups at the purine 6 position and N-arylureas combined with halogens or alkynyl chains at the 2 position have been synthesized and tested for affinity at A1 and A2A adenosine receptors in rat brain membranes and at cloned rat A3 receptors expressed in CHO cells. The derivatives contained the 5‘ substituent found in the potent, nonselective agonist 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-β-d-ribofuranuronamide (NECA). While the carboxamido derivatives (9−13) showed affinity for A1 receptors, the urea derivatives (30−45) showed different degrees of affinity and selectivity for the A3 adenosine receptor subtype. In particular the derivative bearing a p-sulfonamidophenyl-urea at the 6 position, 31 showed a high affinity (Ki = 9 nM) and selectivity for the A3 receptors compared to that of the reference compound 1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-β-d-ribof... |
| Databáze: | OpenAIRE |
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