Potent oxadiazole CGRP receptor antagonists for the potential treatment of migraine

A pharmacophore model was built, based on known CGRP receptor antagonists, and this was used to aid the identification of novel leads. Analogues were designed, modelled and synthesised which incorporated alternative ‘LHS’ fragments linked via either an amide or urea to a privileged ‘RHS’ fragment commonly found in CGRP receptor antagonists. As a result a novel series of oxadiazole CGRP receptor antagonists has been identified and the subsequent optimisation to enhance both potency and bioavailability is presented.

Using a pharmacophore model, based on known CGRP receptor antagonists, a novel series of oxadiazole CGRP receptor antagonists has been identified and the subsequent optimisation to enhance both potency and bioavailability is presented.Figure optionsDownload as PowerPoint slide