Acta Crystallographica Section B

Structural Science

Volume 61, Part 5 (October 2005)

research papers

Acta Cryst. (2005). B61, 569-576 [ doi:10.1107/S0108768105021312 ]

A structural study of new potent and selective antagonists to the A_2B adenosine receptor

V. Ferretti, L. Pretto, M. A. Tabrizi and V. Bertolasi

Abstract: Xanthines, including the natural derivatives theophylline and caffeine, are non-selective antagonists of adenosine. They are able to bind with good affinity to all four adenosine-receptor subtypes A₁, A_2A, A_2B and A₃. In order to develop new drugs with few side effects, over the last few years many efforts have been devoted to the discovery of new adenosine antagonists with enhanced selectivity properties. The present paper reports the crystal structures of five new xanthinic derivatives, which display different affinities and selectivity properties towards the A_2B receptor. Besides the crystallographic study, a structural comparison has been made with the calculated geometry of other xanthinic derivatives which are reported to have similar biological characteristics to understand the structural features controlling their affinity capabilities and selectivity. This structural comparison has been interpreted in the light of a recently published study on the binding of N-benzo[1,3]-dioxol-5-yl-2-[5-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)-1-methyl-1-H-pyrazol-3-iloxy]-acetamide to a model of the A_2B receptor, which shows the most interesting affinity and selectivity properties.

Keywords: adenosine antagonists; affinity; selectivity; xanthines.


	Structure factor file (CIF format) (326.6 kbytes) Contains datablock 1

	Structure factor file (CIF format) (333.4 kbytes) Contains datablock 2

	Structure factor file (CIF format) (243.0 kbytes) Contains datablock 3

	Structure factor file (CIF format) (336.1 kbytes) Contains datablock 4

	Structure factor file (CIF format) (277.1 kbytes) Contains datablock 5

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