S-Benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3-dioxygenase

S-Benzylisothiourea 3a was discovered by its ability to inhibit indoleamine-2,3-dioxygenase (IDO) in our screening program. Subsequent optimization of the initial hit 3a lead to the identification of sub-μM inhibitors 3r and 10h, both of which suppressed kynurenine production in A431 cells. Synthesis and structure–activity relationship of S-benzylisothiourea analogues as small-molecule inhibitors of IDO are described.

Graphical abstractSynthesis and structure–activity relationship of S-benzylisothiourea analogues as small-molecule inhibitors of indoleamine-2,3-dioxygenase are described.Figure optionsDownload full-size imageDownload as PowerPoint slide