title: Identification of cyclicsulfonamide derivatives with an acetamide group as 11β-hydroxysteroid dehydrogenase 1 inhibitors.
abstract: In the continuation of our 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor research, cyclic sulfonamide derivatives with an acetamide group at the 2-position were synthesized and evaluated for their abilities to inhibit 11β-HSD1. Among this series, Compound 34 showed good in vitro activity toward human 11β-HSD1, selectivity against 11β-HSD2, microsomal stability, good pharmacokinetic and safety profiles human ether-a-go-go related gene (hERG and cytochrome P450 (CYP)). Also, a docking study explained the activity difference between human and mouse 11β-HSD1.
authors.affiliation: Department of Chemistry, Korea University, Seoul, Korea.
authors.forename: Se Hoan
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Kwon
authors.forename: So Young
authors.initials: SY
authors.lastname: Chu
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Lee
authors.forename: Banda
authors.initials: B
authors.lastname: Narsaiah
authors.forename: Chi Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Kang
authors.forename: Nam Sook
authors.initials: NS
authors.lastname: Kang
authors.forename: Sang Dal
authors.initials: SD
authors.lastname: Rhee
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Duck Chan
authors.initials: DC
authors.lastname: Ha
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Ahn
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000081:Acetamides / Q000737:chemistry*; D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D000072237:ERG1 Potassium Channel; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D051379:Mice; D013449:Sulfonamides / Q000737:chemistry*; D013843:Thiazines / Q000737:chemistry*
chemical_list: C557625:2-(3-benzoyl-4-hydroxy-1,1-dioxido-2H-benzo(e)(1,2)thiazin-2-yl)-N- (3-(trifluoromethyl)phenyl)acetamide; D000081:Acetamides; D065607:Cytochrome P-450 Enzyme Inhibitors; D000072237:ERG1 Potassium Channel; D004791:Enzyme Inhibitors; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D013449:Sulfonamides; D013843:Thiazines; C030686:acetamide; D003577:Cytochrome P-450 Enzyme System; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2