2-( S )-Phenethylaminothiazolones as Potent, Orally Efficacious Inhibitors of 11β-Hydroxysteriod Dehydrogenase Type 1
2007; American Chemical Society; Volume: 50; Issue: 3 Linguagem: Inglês
10.1021/jm061214f
ISSN1520-4804
AutoresDavid J. St. Jean, Chester Yuan, Eric A. Bercot, Rod Cupples, Michelle Chen, Jenne Fretland, Clarence Hale, Randall W. Hungate, Renée Komorowski, Murielle M. Véniant, Minghan Wang, Xiping Zhang, Christopher Fotsch,
Tópico(s)Pharmacogenetics and Drug Metabolism
Resumo11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is the enzyme that converts cortisone to cortisol. A growing body of evidence suggests that selective inhibition of 11β-HSD1 could potentially treat metabolic syndrome as well as type 2 diabetes. Through modification of our initial lead 1, we have discovered trifluoromethyl thiazolone 17. This compound had a Ki of 22 nM, possessed low in vivo clearance, and showed a 91% inhibition of adipose 11β-HSD1 enzymatic activity in a mouse ex vivo pharmacodynamic model.
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