Usha R. Patel

Substituted pyrazoles as novel sEH antagonist: investigation of key binding interactions within the catalytic domain.

A novel series of pyrazole sEH inhibitors is reported. Lead optimization efforts to replace the aniline core are also described. In particular, 2-pyridine, 3-pyridine and pyridazine analogs are potent sEH inhibitors with favorable CYP3A4 inhibitory and microsomal stability profiles.

Optimization of drug-like properties of nonsteroidal glucocorticoid mimetics and identification of a clinical candidate.

A series of nonsteroidal dissociated glucocorticoid receptor agonists was optimized for drug-like properties such as cytochrome P450 inhibition, metabolic stability, aqueous solubility, and hERG ion channel inhibition. This effort culminated in the identification of the clinical candidate compound ( R )-39.

Discovery and characterization of the N-phenyl-N′-naphthylurea class of p38 kinase inhibitors

An effort aimed at exploring structural diversity in the N-pyrazole-N-naphthylurea class of p38 kinase inhibitors led to the synthesis and characterization of N-phenyl-N-naphthylureas. Examples of these compounds displayed excellent inhibition of TNF-alpha production in vitro, as well as efficacy in a mouse model of lipopolysaccharide induced endotoxemia. In addition, perspective is provided on the role of a sulfonamide functionality in defining inhibitor potency.