N⁶-Cyclopentyl-3-substituted-xylofuranosyladenosines: A New Class of Non-Xanthine Adenosine A1 Receptor Antagonists

التفاصيل البيبلوغرافية
العنوان:	N⁶-Cyclopentyl-3-substituted-xylofuranosyladenosines: A New Class of Non-Xanthine Adenosine A1 Receptor Antagonists
المؤلفون:	Calenbergh, S. Van, Kunzel, von Frijtag Drabbe, K., J., Blaton, N. M., Peeters, O. M., Rozenski, J., Aerschot, A. V., Bruyn, A. De, Keukeleire, D. De, IJzerman, A. P., Herdewijn, P.
المصدر:	Journal of Medicinal Chemistry; November 7, 1997, Vol. 40 Issue: 23 p3765-3772, 8p
مستخلص:	The present study explores the C-3 site of the 3-deoxy-3-xylofuranosyl ring of nucleoside analogues with an adenine or N⁶-cyclopentyladenine (CPA) base moiety and evaluates the effect on adenosine receptor affinity. Two series of sugar-modified adenosines, i.e., 3-amido-3-deoxyadenosines and 3-amidated 3-deoxyxylofuranosyladenines, were synthesized and tested for their affinity at A1 and A2a receptors in rat brain cortex and rat striatum, respectively. The modest affinity found in the xylo series prompted us to synthesize the corresponding N⁶-cyclopentyl derivatives, which proved to be well accommodated by the A1 receptors with potencies in the lower nanomolar range. This represents a new perspective in the purinergic field. The absence of a GTP-induced shift, i.e., the ratio between the affinities measured in the presence and absence of 1 mM GTP indicates an antagonistic behavior of this new class of CPA analogues.
قاعدة البيانات:	Supplemental Index

الوصف
تدمد:	00222623 15204804

N6-Cyclopentyl-3-substituted-xylofuranosyladenosines: A New Class of Non-Xanthine Adenosine A1 Receptor Antagonists