Discovery of 2-Alkyl-1-arylsulfonylprolinamides as 11尾-Hydroxysteroid Dehydrogenase Type 1 Inhibitors
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- 作者：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
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：October 11, 2012
- 年：2012
- 卷：3
- 期：10
- 页码：793-798
- 全文大小：351K
- 年卷期：v.3,no.10(October 11, 2012)
- ISSN：1948-5875
文摘
On the basis of scaffold hopping, a novel series of 2-alkyl-1-arylsulfonylprolinamides was discovered as 11尾-hydroxysteroid dehydrogenase type 1 (11尾-HSD-1) inhibitors. A representative compound 4ek, obtained through SAR and structure optimization studies, demonstrates excellent in vitro potency against 11尾-HSD-1 and dose-dependent in vivo inhibition of 11尾-HSD-1 in a prednisone/prednisolone transformation biomarker study in mice.