Synthesis and evaluation of methoxy substituted 2-benzoyl-1-benzofuran derivatives as lead compounds for the development adenosine A and/or A receptor antagonists.

A series of fourteen methoxy substituted 2-benzoyl-1-benzofuran derivatives were synthesised and their affinities determined for adenosine A and A receptors via radioligand binding assays to establish the structure activity relationships pertinent for A and A affinity. Compound 3j (6,7-dimethoxybenzofuran-2-yl)(3-methoxyphenyl)methanone exhibited A affinity (AK (rat) = 6.880 µM) as well as A affinity (AK (rat) = 0.5161 µM). Compounds 3a-b &3i-k exhibited selective affinity towards A with K values below 10 µM. The results indicate that C6,7-diOCH substitution on ring A in combination with meta (C3')-OCH substitution on ring B is beneficial for A and A affinity and activity. Compounds 3a-b &3j-k showed low cytotoxicity. Upon in vitro and in silico evaluation, compound 3j may be considered lead-like (i.e. a molecular entity suitable for optimization) and, thus, of value in the design of novel, potent and selective adenosine A and A receptor antagonists.