Document Report Card

ID: ALA2151015

Journal: J Med Chem

Title: Discovery of a potent, selective, and orally bioavailable acidic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor: discovery of 2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid (AZD4017).

Authors: Scott JS, Bowker SS, Deschoolmeester J, Gerhardt S, Hargreaves D, Kilgour E, Lloyd A, Mayers RM, McCoull W, Newcombe NJ, Ogg D, Packer MJ, Rees A, Revill J, Schofield P, Selmi N, Swales JG, Whittamore PR.

Abstract: Inhibition of 11β-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound 11i (AZD4017) is an effective inhibitor of 11β-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development.

CiteXplore: 22691057

DOI: 10.1021/jm300592r