title: Synthesis and biological evaluation of sulfonamidooxazoles and beta-keto sulfones: selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
abstract: The design, synthesis, and biological evaluation of arylsulfonamidooxazoles as 11beta-HSD1 inhibitors and the serendipitous discovery of beta-keto sulfones as potent 11beta-HSD1 inhibitors are described here. These two classes of compounds are not active against 11beta-HSD2 and therefore may have significant therapeutic potential for metabolic syndrome, type 2 diabetes and related metabolic dysfunctions.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, MA 02140, USA. jxiang@wyeth.com
authors.forename: Jason
authors.initials: J
authors.lastname: Xiang
authors.forename: Manus
authors.initials: M
authors.lastname: Ipek
authors.forename: Vipin
authors.initials: V
authors.lastname: Suri
authors.forename: Walt
authors.initials: W
authors.lastname: Massefski
authors.forename: Ning
authors.initials: N
authors.lastname: Pan
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
authors.forename: May
authors.initials: M
authors.lastname: Tam
authors.forename: Yuzhe
authors.initials: Y
authors.lastname: Xing
authors.forename: James F
authors.initials: JF
authors.lastname: Tobin
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Steve
authors.initials: S
authors.lastname: Tam
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010080:Oxazoles; D013450:Sulfones; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1