Synthesis and investigations of double-pharmacophore ligands for treatment of chronic and neuropathic pain

Ruben Vardanyan, Gokhale Vijay, Gary S. Nichol, Lu Liu, Isuru Kumarasinghe, Peg Davis, Todd Vanderah, Frank Porreca, Josephine Lai, Victor J. Hruby

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Acids 9a-f as possible bivalent ligands designed as a structural combination of opioid μ-agonist (Fentanyl) and NSAID (Indomethacin) activities and produced compounds which were tested as analgesics. The obtained series of compounds exhibits low affinity and activity both at opioid receptors and as cyclooxygenase (COX) inhibitors. One explanation of the weak opioid activity could be stereochemical peculiarities of these bivalent compounds which differ significantly from the fentanyl skeleton. The absence of significant COX inhibitory properties could be explained by the required substitution of an acyl fragment in the indomethacin structure for 4-piperidyl.

Original languageEnglish (US)
Pages (from-to)5044-5053
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number14
DOIs
StatePublished - Jul 15 2009

Keywords

  • Analgesics
  • Indole
  • NSAID
  • Opioids
  • Piperidine

ASJC Scopus subject areas

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

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