Michael Philip Clark

The development of new triazole based inhibitors of tumor necrosis factor-α (TNF-α) production

4-Aryl-3-pyridyl and 4-aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel isoxazolone five-membered heterocyclic core are described. Many showed sub-micromolar activity against lipopolysaccharide-induced TNF-alpha production.

Pyrazolones as therapeutics for kinase-mediated inflammatory disorders

Many of the current approaches toward therapies for inflammatory diseases target the inhibition of various kinases. Overexpression or inappropriate activation of these kinases is known to trigger various inflammatory diseases via aberrant phosphorylation of protein targets, including inflammatory diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and inflammatory bowel disease (IBD). A series of pyrazolone-based kinase inhibitors are presented with some biological data for a few of the representative compounds. These publications demonstrate the versatility of the pyrazolone heterocycle as an ATP mimetic.