Synthesis of a series of 8-(substituted-phenyl)xanthines and a study on the effects of substitution pattern of phenyl substituents on affinity for adenosine A(1) and A(2A) receptors

R. Bansal, G. Kumar, D. Gandhi, Louise C. Young, A.L. Harvey

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A new series of 8-(substituted-phenyl)xanthines have been synthesized and compounds were evaluated for their affinity for A(1) and A(2) adenosine receptors (AR) using radioligand binding assays. The effects of varying the positions of 8-phenyl substituents on affinity and selectivity at A(1) and A(2A) adenosine receptors have been studied. Isovanilloid 1,3-dimethyl-8-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenylxanthine (9d) displayed the highest affinity and selectivity towards A(2A) AR subtypes with K-i = 100 nM over A(1) receptors (Ki > 100 mM). It has been observed that substitution pattern on 8-phenyl group greatly affects the affinity and selectivity at adenosine receptors, with A(2A) tolerating bulkier substituents than did A(1) receptors.
Original languageEnglish
Pages (from-to)2122-2127
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Issue number5
Publication statusPublished - May 2009


  • 8-Arylxanthines
  • adenosine receptor antagonists
  • radioligand binding assays
  • A(1) and A(2A) adenosine receptors

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