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

52 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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10.1021/jm100982d

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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\}",

year = "2011",

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doi = "10.1021/jm100982d",

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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

N2 - 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.

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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EP - 386

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 1

ER -

Development of potent μ and δ opioid agonists with high lipophilicity

Abstract

ASJC Scopus subject areas

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