Details

Autor(en) / Beteiligte

• Zhuang, Linghang
• Tice, Colin M.
• Xu, Zhenrong
• Zhao, Wei
• Cacatian, Salvacion
• Ye, Yuan-Jie
• Singh, Suresh B.
• Lindblom, Peter
• McKeever, Brian M.
• Krosky, Paula M.
• Zhao, Yi
• Lala, Deepak
• Kruk, Barbara A.
• Meng, Shi
• Howard, Lamont
• Johnson, Judith A.
• Bukhtiyarov, Yuri
• Panemangalore, Reshma
• Guo, Joan
• Guo, Rong
• Himmelsbach, Frank
• Hamilton, Bradford
• Schuler-Metz, Annette
• Schauerte, Heike
• Gregg, Richard
• McGeehan, Gerard M.
• Leftheris, Katerina
• Claremon, David A.

Titel

Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor

Ist Teil von

• Bioorganic & medicinal chemistry, 2017-07, Vol.25 (14), p.3649-3657

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] A potent, in vivo efficacious 11β hydroxysteroid dehydrogenase type 1 (11β HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11β HSD1 activity in human adipocytes with an IC50 of 4.3nM and in primary human adipose tissue with an IC80 of 53nM. Oral administration of 11j to cynomolgus monkey inhibited 11β HSD1 activity in adipose tissue. Compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011.