Details

Autor(en) / Beteiligte

• Venier, Olivier
• Pascal, Cécile
• Braun, Alain
• Namane, Claudie
• Mougenot, Patrick
• Crespin, Olivier
• Pacquet, François
• Mougenot, Cécile
• Monseau, Catherine
• Onofri, Bénédicte
• Dadji-Faïhun, Rommel
• Leger, Céline
• Ben-Hassine, Majdi
• Van-Pham, Thao
• Ragot, Jean-Luc
• Philippo, Christophe
• Farjot, Géraldine
• Noah, Lionel
• Maniani, Karima
• Boutarfa, Asma
• Nicolaï, Eric
• Guillot, Etienne
• Pruniaux, Marie-Pierre
• Güssregen, Stefan
• Engel, Christian
• Coutant, Anne-Laure
• de Miguel, Beatriz
• Castro, Antonio

Titel

Discovery of SAR184841, a potent and long-lasting inhibitor of 11β-hydroxysteroid dehydrogenase type 1, active in a physiopathological animal model of T2D

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2013-04, Vol.23 (8), p.2414-2421

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.