title: Dihydro-pyrano[2,3-b]pyridines and tetrahydro-1,8-naphthyridines as CB1 receptor inverse agonists: synthesis, SAR and biological evaluation.
abstract: Synthesis and structure-activity relationships of cannabinoid-1 receptor (CB1R) inverse agonists based on dihydro-pyrano[2,3-b] pyridine and tetrahydro-1,8-naphtyridine scaffolds are presented. Rat food intake and pharmacokinetic evaluation of 13g, 13i, 13k and 17a revealed these compounds to be highly efficacious orally active modulators of CB1R.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Christina B
authors.initials: CB
authors.lastname: Madsen-Duggan
authors.forename: John S
authors.initials: JS
authors.lastname: Debenham
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Walsh
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Pei
authors.initials: P
authors.lastname: Huo
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.forename: Julie
authors.initials: J
authors.lastname: Lao
authors.forename: Tung M
authors.initials: TM
authors.lastname: Fong
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: 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: Mark T
authors.initials: MT
authors.lastname: Goulet
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004435:Eating; D006801:Humans; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010599:Pharmacokinetics; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000187:drug effects; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000187:drug effects; D013329:Structure-Activity Relationship; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D009287:Naphthyridines; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2