title: Synthesis and 11β hydroxysteroid dehydrogenase 1 inhibition of thiazolidine derivatives with an adamantyl group.
abstract: A new series of thiazolidine derivatives with an adamantyl group was synthesized and evaluated for their ability to inhibit 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). Our initial compound 5a showed a weak inhibitory activity. Significant improvements in potency were achieved by substituent modification. The potent compound 8g (E) showed good in vitro inhibitory activity toward human 11β-HSD1, selectivity toward 11β-HSD2, metabolic stability, pharmacokinetic, and safety profile. Furthermore, this compound significantly inhibited 11β-HSD1 activity in rat and monkey models, and showed improved glycemic control in KKAy mice.
authors.affiliation: Department of Chemistry, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Kwon
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Kang
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Lee
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: Bok
authors.forename: Chi Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Sang
authors.initials: S
authors.lastname: Dal Rhee
authors.forename: Won Hoon
authors.initials: WH
authors.lastname: Jung
authors.forename: Hee Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Song
authors.forename: Duck Chan
authors.initials: DC
authors.lastname: Ha
authors.forename: Hyae Gyoung
authors.initials: HG
authors.lastname: Cheon
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; D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000882:Haplorhini; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D004791:Enzyme Inhibitors; D053778:Thiazolidines; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000218:Adamantane