Synthesis and evaluation of methoxy substituted 2-benzoyl-1-benzofuran derivatives as lead compounds for the development adenosine A1 and/or A2A receptor antagonists.

摘要: Abstract A series of fourteen methoxy substituted 2-benzoyl-1-benzofuran derivatives were synthesised and their affinities determined for adenosine A1 A2A receptors via radioligand binding assays to establish the structure activity relationships pertinent affinity. Compound 3j (6,7-dimethoxybenzofuran-2-yl)(3-methoxyphenyl)methanone exhibited affinity (A1Ki (rat) = 6.880 µM) as well (A2AKi (rat) = 0.5161 µM). Compounds 3a–b & 3i–k selective towards with Ki values below 10 µM. The results indicate that C6,7-diOCH3 substitution on ring in combination meta (C3′)–OCH3 B is beneficial activity. 3j–k showed low cytotoxicity. Upon vitro silico evaluation, compound may be considered lead-like (i.e. a molecular entity suitable optimization) and, thus, value design novel, potent receptor antagonists.