Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595988 | Bioorganic & Medicinal Chemistry Letters | 2013 | 8 Pages |
Abstract
Starting from 11β-HSD1 inhibitors that were active ex vivo but with Cyp 3A4 liability, we obtained a new series of adamantane ureas displaying potent inhibition of both human and rodent 11β-HSD1 enzymes, devoid of Cyp 3A4 interactions, and rationally designed to provide long-lasting inhibition in target tissues. Final optimizations lead to SAR184841 with good oral pharmacokinetic properties showing in vivo activity and improvement of metabolic parameters in a physiopathological model of type 2 diabetes.
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Authors
Olivier Venier, Cécile Pascal, Alain Braun, Claudie Namane, Patrick Mougenot, Olivier Crespin, François Pacquet, Cécile Mougenot, Catherine Monseau, Bénédicte Onofri, Rommel Dadji-Faïhun, Céline Leger, Majdi Ben-Hassine, Thao Van-Pham,