title: Synthesis of functionalized 1,8-naphthyridinones and their evaluation as novel, orally active CB1 receptor inverse agonists.
abstract: Synthesis, SAR, and binding affinities are described for a new class of 1,8-naphthyridinone CB1 receptor specific inverse agonists. Food intake, knockout mouse, and pharmacokinetic evaluation of 14 indicate that this compound is an effective orally active modulator of CB1.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. john_debenham@merck.com
authors.forename: John S
authors.initials: JS
authors.lastname: Debenham
authors.forename: Christina B
authors.initials: CB
authors.lastname: Madsen-Duggan
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Walsh
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.forename: George A
authors.initials: GA
authors.lastname: Doss
authors.forename: Julie
authors.initials: J
authors.lastname: Lao
authors.forename: Tung M
authors.initials: TM
authors.lastname: Fong
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Schaeffer
authors.forename: Jing Chen
authors.initials: JC
authors.lastname: Xiao
authors.forename: Cathy R-R C
authors.initials: CR
authors.lastname: Huang
authors.forename: Chun-Pyn
authors.initials: CP
authors.lastname: Shen
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Marsh
authors.forename: D Sloan
authors.initials: DS
authors.lastname: Stribling
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Shearman
authors.forename: Alison M
authors.initials: AM
authors.lastname: Strack
authors.forename: D Euan
authors.initials: DE
authors.lastname: MacIntyre
authors.forename: Lex H T
authors.initials: LH
authors.lastname: Van der Ploeg
authors.forename: Mark T
authors.initials: MT
authors.lastname: Goulet
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites; D004435:Eating / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D008956:Models, Chemical; D009287:Naphthyridines / Q000138:chemical synthesis; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors*
chemical_list: D009287:Naphthyridines; D043884:Receptor, Cannabinoid, CB1