title: Arylpropionylpiperazines as antagonists of the human melanocortin-4 receptor.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., San Diego, CA 92130, USA.
authors.forename: Wanlong
authors.initials: W
authors.lastname: Jiang
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Tucci
authors.forename: Caroline W
authors.initials: CW
authors.lastname: Chen
authors.forename: Melissa
authors.initials: M
authors.lastname: Arellano
authors.forename: Joe A
authors.initials: JA
authors.lastname: Tran
authors.forename: Nicole S
authors.initials: NS
authors.lastname: White
authors.forename: Dragan
authors.initials: D
authors.lastname: Marinkovic
authors.forename: Joseph
authors.initials: J
authors.lastname: Pontillo
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fleck
authors.forename: Jenny
authors.initials: J
authors.lastname: Wen
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Ajay
authors.initials: A
authors.lastname: Madan
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; 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
chemical_list: D001596:Benzylamines; C470072:MC4R protein, human; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4; D000077489:Piperazine; C030796:benzylamine