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 S 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 S Vardanyan, Victor J Hruby

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

51 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 Vardanyan, {Ruben S} 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 S

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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