Highly potent inhibitors of TNF-α production. Part 2: identification of drug candidates

Metabolic stabilization of the chemical lead 1, which is a structurally novel inhibitor of TNF-α production, was accomplished by introducing a (1S)-methyl group into the optically active backbone. As a result, 2, 3 and 4 were identified as drug candidates and evaluated pharmacologically. The analysis of an active conformer was also carried out.