Matthew J. Laufersweiler

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.

Chemoenzymatic synthesis of functionalized cyclohexylglycines and α-methylcyclohexylglycines via Kazmaier–Claisen rearrangement

The synthesis of homochiral functionalized cyclohexylglycines and alpha-methylcyclohexylglycines via chelated Kazmaier-Claisen rearrangement is described. These were shown to be potent scaffolds for the development of MMP inhibitors.