title: Discovery of 2-Alkyl-1-arylsulfonylprolinamides as 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors.
abstract: 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.
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Yu
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Xia
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ma
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiong
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Central Research Institute, Shanghai Pharmaceutical Holding Co., Ltd. , Building 5, 898 Ha Lei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
authors.forename: Jingkang
authors.initials: J
authors.lastname: Shen
keywords: 11β-hydroxysteroid dehydrogenase type 1; 2-alkylproline; enzyme inhibitor; metabolic syndrome; prolinamide; sulfonamide