Biphenyl-4-ylcarbamoyl thiophene carboxylic acids as potent DHODH inhibitors.

A previously discovered DHODH inhibitor series was improved by replacing a cyclopentene ring by aromatic heterocycles. The compounds were prepared by the directed ortho-metallation procedure. Inhibitory activities were in the low nanomolar range and the compounds show potent immunosuppressive effects on stimulated PBMC’s.