title: Spirocyclic ureas: orally bioavailable 11 beta-HSD1 inhibitors identified by computer-aided drug design.
abstract: Structure-guided drug design led to the identification of a class of spirocyclic ureas which potently inhibit human 11beta-HSD1 in vitro. Lead compound 10j was shown to be orally bioavailable in three species, distributed into adipose tissue in the mouse, and its (R) isomer 10j2 was efficacious in a primate pharmacodynamic model.
authors.affiliation: Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Tice
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Zhenrong
authors.initials: Z
authors.lastname: Xu
authors.forename: Salvacion T
authors.initials: ST
authors.lastname: Cacatian
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simpson
authors.forename: Yuan-Jie
authors.initials: YJ
authors.lastname: Ye
authors.forename: Suresh B
authors.initials: SB
authors.lastname: Singh
authors.forename: Brian M
authors.initials: BM
authors.lastname: McKeever
authors.forename: Peter
authors.initials: P
authors.lastname: Lindblom
authors.forename: Joan
authors.initials: J
authors.lastname: Guo
authors.forename: Paula M
authors.initials: PM
authors.lastname: Krosky
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Kruk
authors.forename: Jennifer
authors.initials: J
authors.lastname: Berbaum
authors.forename: Richard K
authors.initials: RK
authors.lastname: Harrison
authors.forename: Judith J
authors.initials: JJ
authors.lastname: Johnson
authors.forename: Yuri
authors.initials: Y
authors.lastname: Bukhtiyarov
authors.forename: Reshma
authors.initials: R
authors.lastname: Panemangalore
authors.forename: Boyd B
authors.initials: BB
authors.lastname: Scott
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Bruno
authors.forename: Linghang
authors.initials: L
authors.lastname: Zhuang
authors.forename: Gerard M
authors.initials: GM
authors.lastname: McGeehan
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: David A
authors.initials: DA
authors.lastname: Claremon
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001682:Biological Availability; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D014508:Urea / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics*
chemical_list: D014508:Urea; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1