Synthesis and biological evaluation of cyclic sulfamide derivatives as 11β-hydroxysteroid dehydrogenase 1 inhibitors

  • ACS Med Chem Lett. 2012 Jan 17;3(2):88-93. doi: 10.1021/ml200226x.
Se Hoan Kim  1 ,  Ju Han Bok  2 ,  Jae Hong Lee  1 ,  Il Hyang Kim  1 ,  Sung Wook Kwon  1 ,  Gui Bin Lee  2 ,  Seung Kyu Kang  2 ,  Ji Seon Park  2 ,  Won Hoon Jung  2 ,  Hee Yeon Kim  2 ,  Sang Dal Rhee  2 ,  Sung Hoon Ahn  2 ,  Myung Ae Bae  2 ,  Deok Chan Ha  3 ,  Ki Young Kim  2 ,  Jin Hee Ahn  2
Affiliations
  • 1. Bio-Organic Science Division, Korea Research Institute of Chemical Technology , Yuseong-Gu, Daejeon, 305-600, Korea ; Department of Chemistry, Korea University , Sungbuk-gu, Seoul 136-701, Korea.
  • 2. Bio-Organic Science Division, Korea Research Institute of Chemical Technology , Yuseong-Gu, Daejeon, 305-600, Korea.
  • 3. Department of Chemistry, Korea University , Sungbuk-gu, Seoul 136-701, Korea.
PMID: 24900439 DOI: 10.1021/ml200226x
Abstract

A new series of cyclic sulfamide derivatives were synthesized and evaluated for their ability to inhibit 11β-HSD1. Among this series, 18e showed good in vitro activity toward human 11β-HSD1, selectivity against 11β-HSD2, microsomal stability, and pharmacokinetic and safety profiles (hERG, CYP, and acute toxicity). Additionally, 18e exhibited good in vivo efficacy in rat and monkey models.

Keywords
11β-hydroxysteroid dehydrogenase type 1; adamantyl group; antidiabetic agents; cyclic sulfamide; diabetes.