Synthesis and evaluation of 3-aminopropionyl substituted fentanyl analogues for opioid activity

Ravil R. Petrov, Ruben S. Vardanyan, Yeon S. Lee, Shou wu Ma, Peg Davis, Lucinda J. Begay, Josephine Y. Lai, Frank Porreca, Victor J. Hruby

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

An enkephalin analogue coupled to 'aminofentanyl' has been synthesized and tested for biological activities at the μ and δ opioid receptors. Aminofentanyl which represents a structural derivative of fentanyl has been synthesized by acylation of 1-(2-phenethyl)-4-(N-anilino)piperidine with phthaloyl protected β-alaninyl chloride in the presence of DIPEA, followed by deprotection with hydrazine hydrate. Aminofentanyl has also been successfully acylated with ethyl isocyanate, various acid anhydrides, to further investigate structure-activity relationships of these new fentanyl derivatives. Among the new derivatives compound 7 which carries a Tyr-d-Ala-Gly-Phe opioid message sequence showed good opioid affinity (1 nM at both δ and μ opioid receptors) and bioactivity (34.9 nM in MVD and 42 nM in GPI/LMMP bioassays).

Original languageEnglish (US)
Pages (from-to)4946-4950
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number18
DOIs
StatePublished - Sep 15 2006

Keywords

  • Enkephalin analogue
  • Fentanyl derivatives
  • Opioid agonists

ASJC Scopus subject areas

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

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