title: The discovery and optimization of pyrimidinone-containing MCH R1 antagonists.
abstract: Optimization of a series of constrained melanin-concentrating hormone receptor 1 (MCH R1) antagonists has provided compounds with potent and selective MCH R1 activity. Details of the optimization process are provided and the use of one of the compounds in an animal model of diet-induced obesity is presented.
authors.affiliation: Metabolic and Viral Diseases Centre of Excellence for Drug Discovery, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27707, USA. Donald.L.Hertzog@gsk.com
authors.forename: Donald L
authors.initials: DL
authors.lastname: Hertzog
authors.forename: Kamal A
authors.initials: KA
authors.lastname: Al-Barazanji
authors.forename: Eric C
authors.initials: EC
authors.lastname: Bigham
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bishop
authors.forename: Christy S
authors.initials: CS
authors.lastname: Britt
authors.forename: David L
authors.initials: DL
authors.lastname: Carlton
authors.forename: Joel P
authors.initials: JP
authors.lastname: Cooper
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Daniels
authors.forename: Dulce M
authors.initials: DM
authors.lastname: Garrido
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Goetz
authors.forename: Mary K
authors.initials: MK
authors.lastname: Grizzle
authors.forename: Yu C
authors.initials: YC
authors.lastname: Guo
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Handlon
authors.forename: Diane M
authors.initials: DM
authors.lastname: Ignar
authors.forename: Ronda O
authors.initials: RO
authors.lastname: Morgan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Peat
authors.forename: Francis X
authors.initials: FX
authors.lastname: Tavares
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D051379:Mice; D008806:Mice, Inbred AKR; D008958:Models, Molecular; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D011744:Pyrimidinones; D011979:Receptors, Pituitary Hormone; D013438:Sulfhydryl Compounds; C092274:melanin-concentrating hormone receptor