title: Synthesis and optimization of arylsulfonylpiperazines as a novel class of inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1).
abstract: The synthesis and SAR of a series of arylsulfonylpiperazine inhibitors of 11beta-HSD1 are described. Optimization rapidly led to potent, selective, and orally bioavailable inhibitors demonstrating efficacy in a cynomolgus monkey ex vivo enzyme inhibition model.
authors.forename: Daqing
authors.initials: D
authors.lastname: Sun
authors.forename: Zhulun
authors.initials: Z
authors.lastname: Wang
authors.forename: Mario
authors.initials: M
authors.lastname: Cardozo
authors.forename: Rebekah
authors.initials: R
authors.lastname: Choi
authors.forename: Michael
authors.initials: M
authors.lastname: Degraffenreid
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Di
authors.forename: Xiao
authors.initials: X
authors.lastname: He
authors.forename: Juan C
authors.initials: JC
authors.lastname: Jaen
authors.forename: Marc
authors.initials: M
authors.lastname: Labelle
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.forename: Shichang
authors.initials: S
authors.lastname: Miao
authors.forename: Athena
authors.initials: A
authors.lastname: Sudom
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Hua
authors.initials: H
authors.lastname: Tu
authors.forename: Stefania
authors.initials: S
authors.lastname: Ursu
authors.forename: Nigel
authors.initials: N
authors.lastname: Walker
authors.forename: Xuelei
authors.initials: X
authors.lastname: Yan
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Ye
authors.forename: Jay P
authors.initials: JP
authors.lastname: Powers
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D017739:Arylsulfonic Acids / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology; D001682:Biological Availability; D002460:Cell Line; D018360:Crystallography, X-Ray; D004795:Enzyme Stability / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D017739:Arylsulfonic Acids; D010879:Piperazines; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1