Synthesis of 8-(cyclopentyloxy)phenyl substituted xanthine derivatives as adenosine A_2A ligands

Abstract

The present paper describes the synthesis of a series of 8-(cyclopentyloxy)phenylxanthines and their evaluation for affinity for A₁ and A₂ adenosine receptors using radioligand binding assays. The effects of moving the cyclopentyloxy substituent with or without an ortho methoxy group on the various positions of the 8-phenyl ring have been studied. The vanilloid based xanthines 8-[4-(cyclopentyloxy)-3-methoxyphenyl]-1,3-dimethylxanthine (6a) (K _i = 100 nM) and 8-[(4-cyclopentyloxy)-3-methoxyphenyl]-3-methyl-1-pro-pylxanthine (12) (K _i = 150 nM) displayed the highest affinity at A_2A receptors as well as over 1000 fold selectivity over the A₁ adenosine receptor subtype.

Key words

A₁ and A_A2 adenosine receptors - Adenosine receptor antagonists - Antiasthmatics - 8-Arylxanthines, radioligand binding assays

• References

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