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 journalArticle

34 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)382-386
Number of pages5
JournalJournal of Medicinal Chemistry
Volume54
Issue number1
DOIs
StatePublished - Jan 13 2011

Fingerprint

Opioid Analgesics
Ligands
Enkephalins
Halogenation
Opioid Receptors
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Lee, Y. S., Kulkarani, V., Cowell, S. M., Ma, S. W., Davis, P., Hanlon, K. E., ... Hruby, V. J. (2011). Development of potent μ and δ opioid agonists with high lipophilicity. Journal of Medicinal Chemistry, 54(1), 382-386. https://doi.org/10.1021/jm100982d

Development of potent μ and δ opioid agonists with high lipophilicity. / Lee, Yeon Sun; Kulkarani, Vinod; Cowell, Scott M.; Ma, Shou Wu; Davis, Peg; Hanlon, Katherine E.; Vanderah, Todd W; Lai, Josephine; Porreca, Frank; Vardanyan, Ruben S; Hruby, Victor J.

In: Journal of Medicinal Chemistry, Vol. 54, No. 1, 13.01.2011, p. 382-386.

Research output: Contribution to journalArticle

Lee YS, Kulkarani V, Cowell SM, Ma SW, Davis P, Hanlon KE et al. Development of potent μ and δ opioid agonists with high lipophilicity. Journal of Medicinal Chemistry. 2011 Jan 13;54(1):382-386. https://doi.org/10.1021/jm100982d
Lee, Yeon Sun ; Kulkarani, Vinod ; Cowell, Scott M. ; Ma, Shou Wu ; Davis, Peg ; Hanlon, Katherine E. ; Vanderah, Todd W ; Lai, Josephine ; Porreca, Frank ; Vardanyan, Ruben S ; Hruby, Victor J. / Development of potent μ and δ opioid agonists with high lipophilicity. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 1. pp. 382-386.
@article{6009d224daaa4316b5f16ee108dcb9d3,
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",
month = "1",
day = "13",
doi = "10.1021/jm100982d",
language = "English (US)",
volume = "54",
pages = "382--386",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "1",

}

TY - JOUR

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

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.

UR - http://www.scopus.com/inward/record.url?scp=78651090540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651090540&partnerID=8YFLogxK

U2 - 10.1021/jm100982d

DO - 10.1021/jm100982d

M3 - Article

VL - 54

SP - 382

EP - 386

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 1

ER -