title: Synthesis and SAR of 5,6-diarylpyridines as human CB1 inverse agonists.
abstract: Structure-activity relationship studies for two series of 2-benzyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyridines having either a 3-cyano or 3-carboxamide moiety resulted in the preparation of the 2-(3,4-difluorobenzyloxy)-3-nitrile analog 10d and the 2-(3,4-difluorobenzyloxy)-3-(N-propylcarboxamide) analog 16c, (hCB1 IC(50)=1.3 and 1.7 nM, respectively) as potent and selective hCB1 inverse agonists. Their synthesis and biological activities are described herein.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. laura_meurer@merck.com
authors.forename: Laura C
authors.initials: LC
authors.lastname: Meurer
authors.forename: Paul E
authors.initials: PE
authors.lastname: Finke
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Walsh
authors.forename: Richard B
authors.initials: RB
authors.lastname: Toupence
authors.forename: John S
authors.initials: JS
authors.lastname: Debenham
authors.forename: Mark T
authors.initials: MT
authors.lastname: Goulet
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.forename: Tung M
authors.initials: TM
authors.lastname: Fong
authors.forename: Julie
authors.initials: J
authors.lastname: Lao
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Schaeffer
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Chun-Pyn
authors.initials: CP
authors.lastname: Shen
authors.forename: D
authors.initials: D
authors.lastname: Sloan Stribling
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Shearman
authors.forename: Alison M
authors.initials: AM
authors.lastname: Strack
authors.forename: Lex H T
authors.initials: LH
authors.lastname: Van der Ploeg
mesh_terms: D000818:Animals; D001682:Biological Availability; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1