title: Novel sulfamoyl benzamides as selective CB(2) agonists with improved in vitro metabolic stability.
abstract: A lead optimization campaign in our previously reported sulfamoyl benzamide class of CB(2) agonists was conducted to improve the in vitro metabolic stability profile in this series while retaining high potency and selectivity for the CB(2) receptor. From this study, compound 14, N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide, was identified as a potent and selective CB(2) agonist exhibiting moderate in vitro metabolic stability and oral bioavailability. Compound 14 demonstrated in vivo efficacy in a rat model of post-surgical pain.
authors.affiliation: Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Sellitto
authors.forename: Bertrand
authors.initials: B
authors.lastname: Le Bourdonnec
authors.forename: Karin
authors.initials: K
authors.lastname: Worm
authors.forename: Allan
authors.initials: A
authors.lastname: Goodman
authors.forename: Markku A
authors.initials: MA
authors.lastname: Savolainen
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Chu
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ajello
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Saeui
authors.forename: Lara K
authors.initials: LK
authors.lastname: Leister
authors.forename: Joel A
authors.initials: JA
authors.lastname: Cassel
authors.forename: Robert N
authors.initials: RN
authors.lastname: Dehaven
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Labuda
authors.forename: Michael
authors.initials: M
authors.lastname: Koblish
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Little
authors.forename: Bernice L
authors.initials: BL
authors.lastname: Brogdon
authors.forename: Steven A
authors.initials: SA
authors.lastname: Smith
authors.forename: Roland E
authors.initials: RE
authors.lastname: Dolle
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000814:Aniline Compounds; D001549:Benzamides; C549139:N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides