Development of novel enkephalin analogues that have enhanced opioid activities at both μ and δ opioid receptors

Sun Lee Yeon, Ravil Petrov, Chad K. Park, Shou Wu Ma, Peg Davis, Josephine Lai, Frank Porreca, Ruben S Vardanyan, Victor J Hruby

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Enkephalin analogues with a 4-anilidopiperidine scaffold have been designed and synthesized to achieve therapeutic benefit for the treatment of pain due to mixed μ and δ opioid agonist activities. Ligand 16, in which a Dmt-substituted enkephalin-like structure was linked to the N-phenyl-N- piperidin-4-yl propionamide moiety, showed very high binding affinities (0.4 nM) at μ and δ receptors with an increased hydrophobicity (aLogP = 2.96). This novel lead compound was found to have very potent agonist activities in MVD (1.8 nM) and GPI (8.5 nM) assays.

Original languageEnglish (US)
Pages (from-to)5528-5532
Number of pages5
JournalJournal of Medicinal Chemistry
Volume50
Issue number22
DOIs
StatePublished - Nov 1 2007

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Enkephalins
Opioid Receptors
Opioid Analgesics
Lead compounds
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Scaffolds
Assays
Ligands
Pain
Therapeutics
propionamide
4-anilidopiperidine
Lead

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Development of novel enkephalin analogues that have enhanced opioid activities at both μ and δ opioid receptors. / Yeon, Sun Lee; Petrov, Ravil; Park, Chad K.; Ma, Shou Wu; Davis, Peg; Lai, Josephine; Porreca, Frank; Vardanyan, Ruben S; Hruby, Victor J.

In: Journal of Medicinal Chemistry, Vol. 50, No. 22, 01.11.2007, p. 5528-5532.

Research output: Contribution to journalArticle

Yeon, Sun Lee ; Petrov, Ravil ; Park, Chad K. ; Ma, Shou Wu ; Davis, Peg ; Lai, Josephine ; Porreca, Frank ; Vardanyan, Ruben S ; Hruby, Victor J. / Development of novel enkephalin analogues that have enhanced opioid activities at both μ and δ opioid receptors. In: Journal of Medicinal Chemistry. 2007 ; Vol. 50, No. 22. pp. 5528-5532.
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