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Discovery of 2‑Alkyl-1-arylsulfonylprolinamides as 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors

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journal contribution
posted on 11.10.2012, 00:00 by Jianxin Yu, Haiyan Liu, Guangxin Xia, Lin Liu, Zhenmin Xu, Qian Chen, Chen Ma, Xing Sun, Jiajun Xu, Hua Li, Ping Li, Yufang Shi, Bing Xiong, Xuejun Liu, Jingkang Shen
On the basis of scaffold hopping, a novel series of 2-alkyl-1-arylsulfonylprolinamides was discovered as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) inhibitors. A representative compound 4ek, obtained through SAR and structure optimization studies, demonstrates excellent in vitro potency against 11β-HSD-1 and dose-dependent in vivo inhibition of 11β-HSD-1 in a prednisone/prednisolone transformation biomarker study in mice.

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