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

Organic & Biomolecular Chemistry Pub Date: 2008-07-23 DOI: 10.1039/B807648K

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.

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