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New 2,N6-Disubstituted adenosines: potent and selective A1 adenosine receptor agonists by Sally A Hutchinson; Stephen P Baker; Peter J Scammells is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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A number of adenosine analogues substituted in the 2-and N 6 -positions were synthesized and evaluated for affinity, functional potency and intrinsic activity at the A 1 and A 2A adenosine receptors (AR). Three classes of N 6 -substituents were tested; norbornen-2-yl (series 1), norborn-2-yl (series 2) and 5,6-epoxynorborn-2-yl (series 3). The halogens; fluoro, bromo, and iodo were evaluated as C-2 substituents. All compounds showed relatively high affinity (nanomolar) for the A 1 AR and high potency for inhibiting (À)isoproterenol-stimulated cAMP accumulation in hamster smooth muscle DDT 1 MF-2 cells with the 2-fluoro derivatives from each series having the highest affinity. All of the derivatives showed the same intrinsic activity as CPA. At the A 2A AR, all of the derivatives showed relatively low affinity and potency (micromolar) for stimulating cAMP accumulation in rat pheochromocytoma PC-12 cells. The intrinsic activity of the derivatives compared to CGS 21680 was dependent upon the halogen substituent in the C-2 position with most showing partial agonist activity. Of particular interest is 2-iodo-N 6 -(2S-endo-norborn-2yl)adenosine (5e), which is over 100-fold selective for

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Author

Sally A Hutchinson; Stephen P Baker; Peter J Scammells

Publisher

Elsevier Science; Elsevier ; Elsevier Ltd.; Elsevier BV (ISSN 0968-0896)

Published

2002

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)