Bioisosteric replacement of the pyrazole 3-carboxamide moiety of rimonabant. A novel series of oxadiazoles as CB1 cannabinoid receptor antagonists

Abstract

Based on the bioisosteric replacement of the pyrazole C3-carboxamide of rimonabant with a 5-alkyl oxadiazole ring, a novel class of oxadiazole derivatives with promising biological activity towards CB1 receptors was discovered. Among them, compounds with an alkyl linker containing a strong electron-withdrawing group (e.g., CF₃) and a sterically favorable bulky group (e.g., t-butyl) exhibited excellent CB1 antagonism and selectivity, and thus might serve as potential candidates for further development as anti-obesity agents.