Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB 2 receptor agonists for pain management

Derek W. Nelson*, Jennifer M. Frost, Karin R. Tietje, Alan S. Florjancic, Keith Ryther, William A. Carroll, Michael J. Dart, Anthony V. Daza, Bradley A. Hooker, George K. Grayson, Yihong Fan, Tiffany R. Garrison, Odile F. El-Kouhen, Betty Yao, Madhavi Pai, Prasant Chandran, Chang Zhu, Gin C. Hsieh, Michael D. Meyer

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2604-2608
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number7
DOIs
StatePublished - Apr 1 2012

Keywords

  • CB2 agonists
  • Pain management

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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    Nelson, D. W., Frost, J. M., Tietje, K. R., Florjancic, A. S., Ryther, K., Carroll, W. A., Dart, M. J., Daza, A. V., Hooker, B. A., Grayson, G. K., Fan, Y., Garrison, T. R., El-Kouhen, O. F., Yao, B., Pai, M., Chandran, P., Zhu, C., Hsieh, G. C., & Meyer, M. D. (2012). Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB 2 receptor agonists for pain management Bioorganic and Medicinal Chemistry Letters, 22(7), 2604-2608. https://doi.org/10.1016/j.bmcl.2012.01.121