Roger G. Bookland

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.

The development of new carboxylic acid-based MMP inhibitors derived from a cyclohexylglycine scaffold.

A series of carboxylic acids was prepared based on cyclohexylglycine scaffolds and tested for potency as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for five enzymes within the MMP family, and a number of inhibitors such as compound 18 display low nanomolar potency for MMP-2 and MMP-13, while selectively sparing MMP-1 and MMP-7.

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.