Discovery of Carbono(di)thioates as Indoleamine 2,3-Dioxygenase 1 Inhibitors.

A structure-activity relationship study unexpectedly showed that carbonothioates and , obtained by a unique alkaline hydrolysis of 2-alkylthio-oxazolines and , respectively, are a novel scaffold for indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors. Derivatization of the carbonothioates enhanced inhibitory activity against IDO1 and cellular kynurenine production without cytotoxicity and led to the discovery of the related scaffolds carbonodithioates and cyanocarbonimidodithioates as IDO1 inhibitors. Incorporation of an OH group provided the most potent analogue .