title: Structure-activity relationships of piperazinebenzylamines as potent and selective agonists of the human melanocortin-4 receptor.
abstract: SAR studies on a series of piperazinebenzenes directed toward the human melanocortin-4 receptor resulted in potent MC4R agonists. Replacement of the triazole moiety of an initial lead 4 by a basic nitrogen baring a lipophilic side-chain increased the binding affinities of these compounds. Analogs bearing an additional hetero-atom in the side-chain possessed good agonist potency. Thus, 11h had a Ki of 11 nM, and 13g exhibited an EC50 of 3.8 nM and a Ki of 6.4 nM.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92121, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pontillo
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Tran
authors.forename: Melissa
authors.initials: M
authors.lastname: Arellano
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fleck
authors.forename: Rajesh
authors.initials: R
authors.lastname: Huntley
authors.forename: Dragan
authors.initials: D
authors.lastname: Marinkovic
authors.forename: Marion
authors.initials: M
authors.lastname: Lanier
authors.forename: Jodie
authors.initials: J
authors.lastname: Nelson
authors.forename: Jessica
authors.initials: J
authors.lastname: Parker
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Tucci
authors.forename: Wanlong
authors.initials: W
authors.lastname: Jiang
authors.forename: Caroline W
authors.initials: CW
authors.lastname: Chen
authors.forename: Nicole S
authors.initials: NS
authors.lastname: White
authors.forename: Alan C
authors.initials: AC
authors.lastname: Foster
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001596:Benzylamines; C470072:MC4R protein, human; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4