title: Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors.
abstract: The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11β-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models.
authors.affiliation: Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. daqings@amgen.com
authors.forename: Daqing
authors.initials: D
authors.lastname: Sun
authors.forename: Zhulun
authors.initials: Z
authors.lastname: Wang
authors.forename: Seb
authors.initials: S
authors.lastname: Caille
authors.forename: Michael
authors.initials: M
authors.lastname: DeGraffenreid
authors.forename: Felix
authors.initials: F
authors.lastname: Gonzalez-Lopez de Turiso
authors.forename: Randall
authors.initials: R
authors.lastname: Hungate
authors.forename: Juan C
authors.initials: JC
authors.lastname: Jaen
authors.forename: Ben
authors.initials: B
authors.lastname: Jiang
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Julian
authors.forename: Ron
authors.initials: R
authors.lastname: Kelly
authors.forename: Dustin L
authors.initials: DL
authors.lastname: McMinn
authors.forename: Jacob
authors.initials: J
authors.lastname: Kaizerman
authors.forename: Yosup
authors.initials: Y
authors.lastname: Rew
authors.forename: Athena
authors.initials: A
authors.lastname: Sudom
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: Maren
authors.initials: M
authors.lastname: Willcockson
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; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008252:Macaca fascicularis; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1