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A Functional Screening of Adenosine Analogues at the Adenosine A2B Receptor: A Search for Potent Agonists |
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| Authors: | Maarten de Zwart Regina Link Jacobien K von Frijtag Drabbe Kunzela Gloria Cristalli Kenneth A Jacobson Andrea Townsend-Nicholson |
| Institution: | 1. Division of Medicinal Chemistry , Leiden/Amsterdam Center for Drug Research Leiden University , P.O. Box 9502, 2300, RA Leiden, The Netherlands;2. Dipartimento di Scienze Chimiche , Università di Camerino , 62032, Camerino, Italy;3. Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, NIH , Bethesda, MD, 20892, USA;4. Garvan Institute of Medical Research, St. Vincent's Hospital , Sydney, 2010, New South Wales, Australia |
| Abstract: | Abstract Various adenosine analogues were tested at the adenosine A2B receptor. Agonist potencies were determined by measuring the cyclic AMP production in Chinese Hamster Ovary cells expressing human A2B receptors. 5′-.N-Substituted carboxamidoadenosines were most potent. 5′-N-Ethylcarboxamidoadenosine (NECA) was most active with an ECso value of 3.1 μM. Other ribose modified derivatives displayed low to negligible activity. Potency was reduced by substitution on the exocyclic amino function (N6) of the purine ring system. The most active N6-substituted derivative N6-methyl-NECA was 5 fold less potent than NECA. C8-and most C2-substituted analogues were virtually inactive. 1-Deaza-analogues had a reduced potency, 3-and 7-deazaanalogues were not active. |
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