Abstract
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 language | English |
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Pages (from-to) | 2122-2127 |
Number of pages | 6 |
Journal | European Journal of Medicinal Chemistry |
Volume | 44 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2009 |
Keywords
- 8-Arylxanthines
- adenosine receptor antagonists
- radioligand binding assays
- A(1) and A(2A) adenosine receptors