Development of potent μ and δ opioid agonists with high lipophilicity

Yeon Sun Lee; Vinod Kulkarani; Scott M. Cowell; Shou Wu Ma; Peg Davis; Katherine E. Hanlon; Todd W. Vanderah; Josephine Lai; Frank Porreca; Ruben Vardanyan; Victor J. Hruby

doi:10.1021/jm100982d

Development of potent μ and δ opioid agonists with high lipophilicity

Yeon Sun Lee, Vinod Kulkarani, Scott M. Cowell, Shou Wu Ma, Peg Davis, Katherine E. Hanlon, Todd W. Vanderah, Josephine Lai, Frank Porreca, Ruben Vardanyan, Victor J. Hruby

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

46 Scopus citations

Abstract

An SAR study on the Dmt-substituted enkephalin-like tetrapeptide with a N-phenyl-N-piperidin-4-ylpropionamide moiety at the C-terminal was performed and has resulted in highly potent ligands at μ and δ opioid receptors. In general, ligands with the substitution of d-Nle² and halogenation of the aromatic ring of Phe⁴ showed highly increased opioid activities. Ligand 6 with good biological activities in vitro demonstrated potent in vivo antihyperalgesic and antiallodynic effects in the tail-flick assay.

Original language	English (US)
Pages (from-to)	382-386
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	54
Issue number	1
DOIs	https://doi.org/10.1021/jm100982d
State	Published - Jan 13 2011

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "Development of potent μ and δ opioid agonists with high lipophilicity",

abstract = "An SAR study on the Dmt-substituted enkephalin-like tetrapeptide with a N-phenyl-N-piperidin-4-ylpropionamide moiety at the C-terminal was performed and has resulted in highly potent ligands at μ and δ opioid receptors. In general, ligands with the substitution of d-Nle2 and halogenation of the aromatic ring of Phe4 showed highly increased opioid activities. Ligand 6 with good biological activities in vitro demonstrated potent in vivo antihyperalgesic and antiallodynic effects in the tail-flick assay.",

author = "Lee, {Yeon Sun} and Vinod Kulkarani and Cowell, {Scott M.} and Ma, {Shou Wu} and Peg Davis and Hanlon, {Katherine E.} and Vanderah, {Todd W.} and Josephine Lai and Frank Porreca and Ruben Vardanyan and Hruby, {Victor J.}",

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doi = "10.1021/jm100982d",

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T1 - Development of potent μ and δ opioid agonists with high lipophilicity

AU - Lee, Yeon Sun

AU - Kulkarani, Vinod

AU - Cowell, Scott M.

AU - Ma, Shou Wu

AU - Davis, Peg

AU - Hanlon, Katherine E.

AU - Vanderah, Todd W.

AU - Lai, Josephine

AU - Porreca, Frank

AU - Vardanyan, Ruben

AU - Hruby, Victor J.

PY - 2011/1/13

Y1 - 2011/1/13

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AB - An SAR study on the Dmt-substituted enkephalin-like tetrapeptide with a N-phenyl-N-piperidin-4-ylpropionamide moiety at the C-terminal was performed and has resulted in highly potent ligands at μ and δ opioid receptors. In general, ligands with the substitution of d-Nle2 and halogenation of the aromatic ring of Phe4 showed highly increased opioid activities. Ligand 6 with good biological activities in vitro demonstrated potent in vivo antihyperalgesic and antiallodynic effects in the tail-flick assay.

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Development of potent μ and δ opioid agonists with high lipophilicity

Abstract

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