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Discovery of 2-Alkyl-1-arylsulfonylprolinamides as 11?-Hydroxysteroid Dehydrogenase Type 1 Inhibitors.

ABSTRACT: On the basis of scaffold hopping, a novel series of 2-alkyl-1-arylsulfonylprolinamides was discovered as 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD-1) inhibitors. A representative compound 4ek, obtained through SAR and structure optimization studies, demonstrates excellent in vitro potency against 11?-HSD-1 and dose-dependent in vivo inhibition of 11?-HSD-1 in a prednisone/prednisolone transformation biomarker study in mice.

SUBMITTER: Yu J

PROVIDER: S-EPMC4025654 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

Yu Jianxin J Liu Haiyan H Xia Guangxin G Liu Lin L Xu Zhenmin Z Chen Qian Q Ma Chen C Sun Xing X Xu Jiajun J Li Hua H Li Ping P Shi Yufang Y Xiong Bing B Liu Xuejun X Shen Jingkang J

ACS medicinal chemistry letters 20120920 10

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. ...[more]

PMID: 24900382

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