Structure-activity relationship of (1-aryl-2-piperazinylethyl)piperazines: antagonists for the AGRP/melanocortin receptor binding.
Agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin action.(1) In the hypothalamus, melanocortin peptide agonists act as satiety-inducing factors that mediate their action through the melanocortin-4 receptor (MC4R) whereas AGRP is an opposing orexigenic agent. Novel inhibitors of the AGRP/MC4 binding based on (piperazinylethyl)piperazines were prepared, and their structure-activity relationship was established.
Arasasingham
Premilla N
PN
Department of Small Molecule Drug Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA.
Fotsch
Christopher
C
Ouyang
Xiaohu
X
Norman
Mark H
MH
Kelly
Michael G
MG
Stark
Kevin L
KL
Karbon
Bill
B
Hale
Clarence
C
Baumgartner
James W
JW
Zambrano
Martha
M
Cheetham
Janet
J
Tamayo
Nuria A
NA
D054369:Agouti-Related Protein; D001665:Binding Sites; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000037:antagonists & inhibitors / Q000378:metabolism
C515198:AGRP protein, human; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D010879:Piperazines; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D000521:alpha-MSH