Arylpropionylpiperazines as antagonists of the human melanocortin-4 receptor.
A series of 3-arylpropionylpiperazines were synthesized as antagonists of the melanocortin-4 receptor. Their potency was found to be increased by replacing the alpha-methyl substituent of the initial lead 11 with a larger s-Bu or i-Bu group. Further potency enhancement was observed when a glycine or beta-alanine was incorporated onto the benzylamine. Some compounds demonstrated good potency, moderate selectivity, and oral bioavailability.
Jiang
Wanlong
W
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., San Diego, CA 92130, USA.
Tucci
Fabio C
FC
Chen
Caroline W
CW
Arellano
Melissa
M
Tran
Joe A
JA
White
Nicole S
NS
Marinkovic
Dragan
D
Pontillo
Joseph
J
Fleck
Beth A
BA
Wen
Jenny
J
Saunders
John
J
Madan
Ajay
A
Foster
Alan C
AC
Chen
Chen
C
D000818:Animals; D001596:Benzylamines / Q000737:chemistry; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D001596:Benzylamines; C470072:MC4R protein, human; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4; D000077489:Piperazine; C030796:benzylamine