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

ABSTRACT: A new series of cyclic sulfamide derivatives were synthesized and evaluated for their ability to inhibit 11?-HSD1. Among this series, 18e showed good in vitro activity toward human 11?-HSD1, selectivity against 11?-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.

SUBMITTER: Kim SH

PROVIDER: S-EPMC4025780 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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

Kim Se Hoan SH Bok Ju Han JH Lee Jae Hong JH Kim Il Hyang IH Kwon Sung Wook SW Lee Gui Bin GB Kang Seung Kyu SK Park Ji Seon JS Jung Won Hoon WH Kim Hee Yeon HY Rhee Sang Dal SD Ahn Sung Hoon SH Bae Myung Ae MA Ha Deok Chan DC Kim Ki Young KY Ahn Jin Hee JH

ACS medicinal chemistry letters 20120117 2

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. ...[more]

PMID: 24900439

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