title: Discovery of 11β-hydroxysteroid dehydrogenase type 1 inhibitor.
abstract: Various adamantane sulfonamides showed potent inhibitory activity against 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In continuation of our efforts to discover a more potent, selective and metabolically stable 11β-HSD1 inhibitor in mice as well as in humans, we optimized the adamantane sulfonamide using structure-based molecular modeling. Compound 3, which has alkyl side chains on the linker, demonstrated a potent inhibitory activity against human and mouse 11β-HSD1 (IC50 of 0.6 nM and 26 nM, respectively) and good physicochemical properties as a new anti-diabetes drug candidate.
authors.affiliation: Institute for New Drug Development, Division of Life Sciences, Incheon National University, Incheon 406-772, Republic of Korea.
authors.forename: Sung Pyo
authors.initials: SP
authors.lastname: Hong
authors.affiliation: Center for Development and Commercialization of Anti Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, 138-736, Republic of Korea.
authors.forename: Ky Youb
authors.initials: KY
authors.lastname: Nam
authors.affiliation: R & D Center, Ahn Gook Pharm., Suwon 443-766, Republic of Korea.
authors.forename: Young June
authors.initials: YJ
authors.lastname: Shin
authors.affiliation: Institute for New Drug Development, Division of Life Sciences, Incheon National University, Incheon 406-772, Republic of Korea.
authors.forename: Kil Won
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Institute for New Drug Development, Division of Life Sciences, Incheon National University, Incheon 406-772, Republic of Korea. Electronic address: skahn@incheon.ac.kr.
authors.forename: Soon Kil
authors.initials: SK
authors.lastname: Ahn
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1
keywords: 11-β-Hydroxysteroid dehydrogenase (11β-HSD1) inhibitor; Adamantane sulfonamide; Antidiabetes; Optimization; Structure-based molecular modeling