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Discovery of camphor-derived pyrazolones as 11β-hydroxysteroid dehydrogenase type 1 inhibitors.

Paul Gillespie,Sherrie Pietranico-Cole,Michael Myers,Joseph A Bilotta,Karin Conde-Knape,Nader Fotouhi,Robert A Goodnow,Kevin R Guertin,Matthew M Hamilton,Nancy-Ellen Haynes,Baolian Liu,Lida Qi,Yonglin Ren,Nathan R Scott,Sung-Sau So,Cheryl Spence,Rebecca Taub,Kshitij Thakkar,Jefferson W Tilley,Catherine Zwingelstein

Bioorganic & Medicinal Chemistry Letters（2014）

Cited 3|Views17
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Abstract
Starting from screening hit, (4S,7R)-1,7,8,8-tetramethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (7), we optimized the potency and pharmacokinetic properties. This led to the identification of compounds with good in vivo activity in a mouse pharmacodynamic model of inhibition of 11βHSD1.
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Key words
11βHSD1,Type 2 diabetes,Hit-to-lead,Pharmacodynamic model
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