1114088-40-2Relevant academic research and scientific papers
Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor
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.
, p. 3649 - 3657 (2017/06/13)
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 4.3?nM and in primary human adipose tissue with an IC80 of 53?nM. 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.
CYCLIC INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1
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Page/Page column 32, (2011/01/05)
This invention relates to novel compounds of the Formula Ik, Im1, Im2, Im5, In1, In2, In5, Io1, Io2, Io5, Ip1, Ip3, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.
