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

A previously discovered DHODH inhibitor series was further improved by replacing the cyclopentene ring by aromatic heterocycles. Different isomers of these compounds were prepared by the directed ortho-metallation procedure. The compounds are more active than the corresponding cyclopentene analogs and show potent effects on PBMC’s proliferation.

Graphical abstractA 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.Figure optionsDownload full-size imageDownload as PowerPoint slide