title: Pyrrolidinones as orally bioavailable antagonists of the human melanocortin-4 receptor with anti-cachectic activity.
abstract: A series of pyrrolidinones derived from phenylalanines were synthesized as potent antagonists of the human melanocortin-4 receptor. These compounds showed high potencies and selectivities, and several of them had good oral bioavailabilities. In addition, 12e demonstrated in vivo efficacy in a murine cachexia model.
authors.affiliation: Department of Medicinal Chemistry, Neurocrine Biosciences Inc, San Diego, CA 92130, USA.
authors.forename: Joe A
authors.initials: JA
authors.lastname: Tran
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Tucci
authors.forename: Wanlong
authors.initials: W
authors.lastname: Jiang
authors.forename: Dragan
authors.initials: D
authors.lastname: Marinkovic
authors.forename: Caroline W
authors.initials: CW
authors.lastname: Chen
authors.forename: Melissa
authors.initials: M
authors.lastname: Arellano
authors.forename: Stacy
authors.initials: S
authors.lastname: Markison
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fleck
authors.forename: Jenny
authors.initials: J
authors.lastname: Wen
authors.forename: Nicole S
authors.initials: NS
authors.lastname: White
authors.forename: Joseph
authors.initials: J
authors.lastname: Pontillo
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Daniel
authors.initials: D
authors.lastname: Marks
authors.forename: Sam R
authors.initials: SR
authors.lastname: Hoare
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: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001823:Body Composition; D001835:Body Weight; D002100:Cachexia / Q000188:drug therapy*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C470072:MC4R protein, human; D011760:Pyrrolidinones; D044105:Receptor, Melanocortin, Type 4