Design, synthesis, and SAR studies on a series of 2-pyridinylpiperazines as potent antagonists of the melanocortin-4 receptor.
A series of 2-pyridinylpiperazines derived from beta-Ala-(2,4-Cl)Phe dipeptide was synthesized for the study of their SARs and possible interactions with the MC4 receptor. Compounds such as 11k (Ki=6.5 nM) possessed high potency.
Tran
Joe A
JA
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Pontillo
Joseph
J
Fleck
Beth A
BA
Marinkovic
Dragan
D
Arellano
Melissa
M
Tucci
Fabio C
FC
Lanier
Marion
M
Saunders
John
J
Jiang
Wanlong
W
Chen
Caroline W
CW
Foster
Alan C
AC
Chen
Chen
C
D004151:Dipeptides / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D015091:beta-Alanine / Q000737:chemistry
D004151:Dipeptides; D010879:Piperazines; D011725:Pyridines; D044105:Receptor, Melanocortin, Type 4; D015091:beta-Alanine