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 Vardanyan; Victor J. Hruby

doi:10.1021/jm061465o

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 Vardanyan, Victor J. Hruby

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

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 language	English (US)
Pages (from-to)	5528-5532
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	50
Issue number	22
DOIs	https://doi.org/10.1021/jm061465o
State	Published - Nov 1 2007

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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

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.",

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T1 - Development of novel enkephalin analogues that have enhanced opioid activities at both μ and δ opioid receptors

AU - Yeon, Sun Lee

AU - Petrov, Ravil

AU - Park, Chad K.

AU - Ma, Shou Wu

AU - Davis, Peg

AU - Lai, Josephine

AU - Porreca, Frank

AU - Vardanyan, Ruben

AU - Hruby, Victor J.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - 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.

AB - 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.

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

Abstract

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