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. 2011 Jan 13;54(1):382-6.
doi: 10.1021/jm100982d. Epub 2010 Dec 3.

Development of potent μ and δ opioid agonists with high lipophilicity

Yeon Sun Lee  1 , 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
Affiliations

Development of potent μ and δ opioid agonists with high lipophilicity

Yeon Sun Lee et al. J Med Chem. .

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-Nle(2) and halogenation of the aromatic ring of Phe(4) 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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Figures

Figure 1
Figure 1. Design of opioid ligands
Figure 2
Figure 2
Antihyperalgesic effects of 6 (i.th.) using radiant heat in L5/L6 SNL-operated male SD rats. Thermal hypersensitivity by paw withdrawal (left) Antinociceptive dose-response curve at 30 min (right)
Figure 3
Figure 3
Antiallodynic effects of 6 (i.th.) using von Frey filaments in L5/L6 SNL-operated male SD rats. Tactile allodynia by paw withdrawal thresholds (left) Antinociceptive dose-response curve at30 min (right)
See this image and copyright information in PMC

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