Synthesis and biological evaluation of new opioid agonist and neurokinin-1 antagonist bivalent ligands

Ruben S Vardanyan, Vlad K. Kumirov, Gary S. Nichol, Peg Davis, Erika Liktor-Busa, David Rankin, Eva Varga, Todd W Vanderah, Frank Porreca, Josephine Lai, Victor J Hruby

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Newly designed bivalent ligands - opioid agonist/NK1-antagonists have been synthesized. The synthesis of new starting materials - carboxy-derivatives of Fentanyl (1a-1c) was developed. These products have been transformed to 'isoimidium perchlorates' (2a-c). The new isoimidium perchlorates have been successfully implemented in nucleophilic addition reactions, with l-tryptophan 3,5-bis(trifluoromethyl)benzyl ester to give the target compounds - amides (3a-c). Perchlorates (2a-c) successfully undergo reactions with other nucleophiles such as alcohols, amines or hydrazines. The obtained compound 3b exhibited μ-opioid agonist activity and NK1-antagonist activity and may serve as a useful lead compound for the further design of a new series of opioid agonist/NK1-antagonist compounds.

Original languageEnglish (US)
Pages (from-to)6135-6142
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number20
DOIs
StatePublished - Oct 15 2011

Fingerprint

Perchlorates
Opioid Analgesics
Ligands
Hydrazines
Lead compounds
Nucleophiles
Addition reactions
Fentanyl
Amides
Tryptophan
Amines
Esters
Alcohols
Derivatives

Keywords

  • μ-Opioids
  • Analgesic
  • Bivalent ligands
  • Fentanyl
  • NK1 antagonist

ASJC Scopus subject areas

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

Cite this

Synthesis and biological evaluation of new opioid agonist and neurokinin-1 antagonist bivalent ligands. / Vardanyan, Ruben S; Kumirov, Vlad K.; Nichol, Gary S.; Davis, Peg; Liktor-Busa, Erika; Rankin, David; Varga, Eva; Vanderah, Todd W; Porreca, Frank; Lai, Josephine; Hruby, Victor J.

In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 20, 15.10.2011, p. 6135-6142.

Research output: Contribution to journalArticle

Vardanyan, Ruben S ; Kumirov, Vlad K. ; Nichol, Gary S. ; Davis, Peg ; Liktor-Busa, Erika ; Rankin, David ; Varga, Eva ; Vanderah, Todd W ; Porreca, Frank ; Lai, Josephine ; Hruby, Victor J. / Synthesis and biological evaluation of new opioid agonist and neurokinin-1 antagonist bivalent ligands. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 20. pp. 6135-6142.
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