Synthesis and cannabinoid activity of a variety of 2,3-substituted 1-benzo[b]thiophen derivatives and 2,3-substituted benzofuran: Novel agonists for the CB₁ receptor

An exploratory chemical effort has been undertaken to develop a novel series of compounds as selective CB₁ agonists. It is hoped that compounds of this type will have clinical utility in pain control and cerebral ischaemia following stroke or traumatic head injury. We report here medicinal chemistry studies directed towards the investigation of several classes of 1-benzo[b]thiophen and benzofuran derivatives as novel CB₁ agonists. We have discovered a novel series of compounds, which contain a 1-benzo[b]thiophen or a benzofuran group as the central aromatic group. Our investigation of this series of compounds has enhanced our understanding of the importance of binding sites within the CB₁ receptor for favourable CB₁ potency. Our understanding of these factors allowed us to modify the structure of a 1-benzothiophen derivative and improve its potency at the CB₁ receptor.