DHODH-IN-12 (Compound 12b) is a Leflunomide derivative and a weak dihydroorotate dehydrogenase (DHODH) inhibitor with a pKa of 5.07.
Designed a compound structurally related to Leflunomide, containing the furazan ring (Compound 12a), is designed. Compound 12a undergo ring 4 scission under physiological pH conditions to afford the corresponding cyano-oximes DHODH-IN-12 (Compound 12b). DHODH-IN-12 has been assayed as a DHODH inhibitor; its low potency is probably due to the unfavourable stereochemistry of the oxime substructure[1].
References:
[1]. Giorgis M, et al. 1,2,5-Oxadiazole analogues of leflunomide and related compounds. Eur J Med Chem. 2011 Jan;46(1):383-92.