Structure-activity relationship of a series of cyclohexylpiperidines bearing an amide side chain as antagonists of the human melanocortin-4 receptor.
A series of cyclohexylpiperazines was synthesized as potent and selective antagonists of the human MC4 receptor. Compound 14t displayed binding affinity (Ki) of 4.2 and 1100 nM at MC4R and MC3R, respectively.
Tran
Joseph A
JA
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Pontillo
Joseph
J
Arellano
Melissa
M
Fleck
Beth A
BA
Tucci
Fabio C
FC
Marinkovic
Dragan
D
Chen
Caroline W
CW
Saunders
John
J
Foster
Alan C
AC
Chen
Chen
C
D000577:Amides / Q000737:chemistry*; D001667:Binding, Competitive; D006801:Humans; D008968:Molecular Conformation; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000577:Amides; C470072:MC4R protein, human; D010880:Piperidines; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4