Crystal and molecular structures of two adenosine receptor ligands: 1,3-dimethylxanthine-7-riboside monohydrate (DMX-7R), a partial A1 agonist, and 9-chloro-2-(furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine methane sulfonate (CGS 15943), a selective A_2a antagonist

Abstract

The structures of two adenosine receptor ligands were determined from single-crystal X-ray diffraction analysis: DMX-7R, 1,3-dimethylxanthine-7-riboside monohydrate, monoclinic P2₁, a = 4.633(2), b = 6.755(1), c = 22.921(3) Å, β = 92.11(3)°, final R = 0.034 for 1441 observed reflections; CGS 15943, 9-chloro-2-(2-furyl)[1,2,4]triazolo[ 1.5-c]quinazolin-5-amine methane sulfonate, monoclinic, P2₁, a = 7.887(3), b = 10.014(2), c = 20.601(5) Å, β = 95.36(3)°, final R = 0.059 for 2150 observed reflections. DMX-7R, a partial A₁ agonist, is a nucleoside which displays an anti conformation around the glycosidic bond and a ³T₂ conformation of the ribose ring. Extensive hydrogen bonds are observed which include all the hydroxyl groups of the ribose, a water molecule and the sp² hybridized N9 atom. CGS 15943 is a selective A_2a antagonist. Its structure presents some analogies with that of adenine. The lack of the ribose ring is a necessary condition for antagonistic activity, while the furane substituent and the fused chloropheny1 ring act as modulators of the A2 selectivity. The molecule, roughly planar, is protonated at the imino nitrogen of the pyrimidine ring and forms strong hydrogen bonds with two oxygens of the methane sulfonate ion.