Structural modifications of N-arylamide oxadiazoles: Identification of N-arylpiperidine oxadiazoles as potent and selective agonists of CB2.
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.
DiMauro
Erin F
EF
Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA. edimauro@amgen.com
Buchanan
John L
JL
Cheng
Alan
A
Emkey
Renee
R
Hitchcock
Stephen A
SA
Huang
Liyue
L
Huang
Ming Y
MY
Janosky
Brett
B
Lee
Josie H
JH
Li
Xingwen
X
Martin
Matthew W
MW
Tomlinson
Susan A
SA
White
Ryan D
RD
Zheng
Xiao Mei
XM
Patel
Vinod F
VF
Fremeau
Robert T
RT
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
D010069:Oxadiazoles; D043885:Receptor, Cannabinoid, CB2