1,2,5-Oxadiazole analogues of leflunomide and related compounds

► 1,2,5-oxadiazole was proposed as a bioisoster of isoxazole in leflunomide analogues. ► Cyano-oximes display weak inhibitory activity on DHODH. ► The feeble inhibitory activity of cyano-oximes is amenable to their E configuration. ► Oxidation of cyano-oximes to related nitro derivatives increases DHODH inhibition.