title: Structure-activity relationship of (1-aryl-2-piperazinylethyl)piperazines: antagonists for the AGRP/melanocortin receptor binding.
abstract: 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.
authors.affiliation: Department of Small Molecule Drug Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA.
authors.forename: Premilla N
authors.initials: PN
authors.lastname: Arasasingham
authors.forename: Christopher
authors.initials: C
authors.lastname: Fotsch
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Ouyang
authors.forename: Mark H
authors.initials: MH
authors.lastname: Norman
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kelly
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Stark
authors.forename: Bill
authors.initials: B
authors.lastname: Karbon
authors.forename: Clarence
authors.initials: C
authors.lastname: Hale
authors.forename: James W
authors.initials: JW
authors.lastname: Baumgartner
authors.forename: Martha
authors.initials: M
authors.lastname: Zambrano
authors.forename: Janet
authors.initials: J
authors.lastname: Cheetham
authors.forename: Nuria A
authors.initials: NA
authors.lastname: Tamayo
mesh_terms: 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
chemical_list: 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