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

21 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
Publication statusPublished - Sep 15 2006

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Keywords

  • Enkephalin analogue
  • Fentanyl derivatives
  • Opioid agonists

ASJC Scopus subject areas

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

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