A Novel Approach for the Synthesis of Peripherally Acting Dual Target Inhibitor of Cannabinoid-1 (CB1 Receptor) and Inducible Nitric Oxide Synthase (iNOS) (S-MRI-1867/Zevaquenabant)

Zevaquenabant (S-MRI-1867) is a clinical-stage agent that is a peripherally restricted, potent antagonist of CB(1)R and an inhibitor of inducible nitric oxide synthase. A novel synthetic route to this highly selective active pharmaceutical agent is described in this paper. This route makes use of rationally installed chiral thio-substituted leaving group derived from a Bunte-salt reaction approach to yield diastereomeric compounds which are further processed to enantiopure compounds. The method will enable a rapid assembly of a variety of chiral sulfonyl amino compounds in this series.