title: Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB₂ receptor agonists for pain management.
abstract: SAR studies on a series of thiophene amide derivatives provided CB(2) receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB(2) over CB(1) effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain. Control experiments using a CB(2) antagonist demonstrated the efficacy in the pain models resulted from CB(2) agonism.
authors.affiliation: Neurological Diseases Research, Global Pharmaceutical R&D, Abbott, 100 Abbott Park Road, Abbott Park, IL 60064, USA. derek.nelson@abbott.com
authors.forename: Derek W
authors.initials: DW
authors.lastname: Nelson
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Frost
authors.forename: Karin R
authors.initials: KR
authors.lastname: Tietje
authors.forename: Alan S
authors.initials: AS
authors.lastname: Florjancic
authors.forename: Keith
authors.initials: K
authors.lastname: Ryther
authors.forename: William A
authors.initials: WA
authors.lastname: Carroll
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dart
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Daza
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Hooker
authors.forename: George K
authors.initials: GK
authors.lastname: Grayson
authors.forename: Yihong
authors.initials: Y
authors.lastname: Fan
authors.forename: Tiffany R
authors.initials: TR
authors.lastname: Garrison
authors.forename: Odile F
authors.initials: OF
authors.lastname: El-Kouhen
authors.forename: Betty
authors.initials: B
authors.lastname: Yao
authors.forename: Madhavi
authors.initials: M
authors.lastname: Pai
authors.forename: Prasant
authors.initials: P
authors.lastname: Chandran
authors.forename: Chang
authors.initials: C
authors.lastname: Zhu
authors.forename: Gin C
authors.initials: GC
authors.lastname: Hsieh
authors.forename: Michael D
authors.initials: MD
authors.lastname: Meyer
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000577:Amides; D000700:Analgesics; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013876:Thiophenes