Literature DB >> 18553955

Discovery of novel, potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) exhibiting oral activity in an enzyme inhibition ex vivo model.

Lisa D Julian1, Zhulun Wang, Tracy Bostick, Seb Caille, Rebekah Choi, Michael DeGraffenreid, Yongmei Di, Xiao He, Randall W Hungate, Juan C Jaen, Jinsong Liu, Mario Monshouwer, Dustin McMinn, Yosup Rew, Athena Sudom, Daqing Sun, Hua Tu, Stefania Ursu, Nigel Walker, Xuelei Yan, Qiuping Ye, Jay P Powers.   

Abstract

We report the discovery of potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2, we discovered pyridyl compound 13. This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11beta-HSD1 activity in a monkey ex vivo pharmacodynamic model.

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Year:  2008        PMID： 18553955     DOI： 10.1021/jm800310g

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  5 in total

1.  On-column ligand exchange for structure-based drug design: a case study with human 11β-hydroxysteroid dehydrogenase type 1.

Authors:  Wenying Qin; Russell A Judge; Kenton L Longenecker; Larry R Solomon; John E Harlan
Journal:  Acta Crystallogr Sect F Struct Biol Cryst Commun       Date:  2012-04-21

Review 2.  Crystal structures of 11β-hydroxysteroid dehydrogenase type 1 and their use in drug discovery.

Authors:  Mark P Thomas; Barry V L Potter
Journal:  Future Med Chem       Date:  2011-03       Impact factor: 3.808

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

Authors:  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
Journal:  ACS Med Chem Lett       Date:  2012-09-20       Impact factor: 4.345

4.  Substrate binding process and mechanistic functioning of type 1 11β-hydroxysteroid dehydrogenase from enhanced sampling methods.

Authors:  Angelo D Favia; Matteo Masetti; Maurizio Recanatini; Andrea Cavalli
Journal:  PLoS One       Date:  2011-09-23       Impact factor: 3.240

5.  Novel small molecule 11β-HSD1 inhibitor from the endophytic fungus Penicillium commune.

Authors:  Weiguang Sun; Xintao Chen; Qingyi Tong; Hucheng Zhu; Yan He; Liang Lei; Yongbo Xue; Guangmin Yao; Zengwei Luo; Jianping Wang; Hua Li; Yonghui Zhang
Journal:  Sci Rep       Date:  2016-05-19       Impact factor: 4.379
  5 in total

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