title: Structural modifications of N-arylamide oxadiazoles: Identification of N-arylpiperidine oxadiazoles as potent and selective agonists of CB2.
abstract: Structural modifications to the central portion of the N-arylamide oxadiazole scaffold led to the identification of N-arylpiperidine oxadiazoles as conformationally constrained analogs that offered improved stability and comparable potency and selectivity. The simple, modular scaffold allowed for the use of expeditious and divergent synthetic routes, which provided two-directional SAR in parallel. Several potent and selective agonists from this novel ligand class are described.
authors.affiliation: Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA. edimauro@amgen.com
authors.forename: Erin F
authors.initials: EF
authors.lastname: DiMauro
authors.forename: John L
authors.initials: JL
authors.lastname: Buchanan
authors.forename: Alan
authors.initials: A
authors.lastname: Cheng
authors.forename: Renee
authors.initials: R
authors.lastname: Emkey
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Hitchcock
authors.forename: Liyue
authors.initials: L
authors.lastname: Huang
authors.forename: Ming Y
authors.initials: MY
authors.lastname: Huang
authors.forename: Brett
authors.initials: B
authors.lastname: Janosky
authors.forename: Josie H
authors.initials: JH
authors.lastname: Lee
authors.forename: Xingwen
authors.initials: X
authors.lastname: Li
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Martin
authors.forename: Susan A
authors.initials: SA
authors.lastname: Tomlinson
authors.forename: Ryan D
authors.initials: RD
authors.lastname: White
authors.forename: Xiao Mei
authors.initials: XM
authors.lastname: Zheng
authors.forename: Vinod F
authors.initials: VF
authors.lastname: Patel
authors.forename: Robert T
authors.initials: RT
authors.lastname: Fremeau
mesh_terms: D000818:Animals; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism*; D008968:Molecular Conformation; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D010069:Oxadiazoles; D043885:Receptor, Cannabinoid, CB2