title: Melanocortin subtype-4 receptor agonists containing a piperazine core with substituted aryl sulfonamides.
abstract: The biological activity for a set of melanocortin-4 receptor (MC4R) agonists containing a piperazine core with an ortho-substituted aryl sulfonamide is described. Compounds from this set had binding and functional activities at MC4R less than 30 nM. The most selective compound in this series was >25,000-fold more potent at MC4R than MC3R, and 490-fold more potent at MC4R than MC5R. This compound also reduced food intake after oral dosing at 25, 50, and 100 mg kg(-1) in fasted mice.
authors.affiliation: Department of Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Mailstop 29-1-B, Thousand Oaks, CA 91320, USA. cfotsch@amgen.com
authors.forename: Christopher
authors.initials: C
authors.lastname: Fotsch
authors.forename: Nianhe
authors.initials: N
authors.lastname: Han
authors.forename: Premilla
authors.initials: P
authors.lastname: Arasasingham
authors.forename: Yunxin
authors.initials: Y
authors.lastname: Bo
authors.forename: Michelle
authors.initials: M
authors.lastname: Carmouche
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: James
authors.initials: J
authors.lastname: Davis
authors.forename: Martin H
authors.initials: MH
authors.lastname: Goldberg
authors.forename: Clarence
authors.initials: C
authors.lastname: Hale
authors.forename: Feng-Yin
authors.initials: FY
authors.lastname: Hsieh
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kelly
authors.forename: Qingyian
authors.initials: Q
authors.lastname: Liu
authors.forename: Mark H
authors.initials: MH
authors.lastname: Norman
authors.forename: Duncan M
authors.initials: DM
authors.lastname: Smith
authors.forename: Markian
authors.initials: M
authors.lastname: Stec
authors.forename: Nuria
authors.initials: N
authors.lastname: Tamayo
authors.forename: Ning
authors.initials: N
authors.lastname: Xi
authors.forename: Shimin
authors.initials: S
authors.lastname: Xu
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Bannon
authors.forename: James W
authors.initials: JW
authors.lastname: Baumgartner
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4; D013449:Sulfonamides