Arizona Health Sciences

Development of potent μ and δ opioid agonists with high lipophilicity.

TitleDevelopment of potent μ and δ opioid agonists with high lipophilicity.
Publication TypeJournal Article
Year of Publication2011
AuthorsLee YSun, Kulkarani V, Cowell SM, Ma S-W, Davis P, Hanlon KE, Vanderah TW, Lai J, Porreca F, Vardanyan R, Hruby VJ
JournalJ Med Chem
Volume54
Issue1
Pagination382-6
Date Published2011 Jan 13
ISSN1520-4804
KeywordsAmides, Analgesics, Opioid, Animals, Binding, Competitive, Cell Membrane Permeability, CHO Cells, Cricetinae, Cricetulus, Humans, Hyperalgesia, Ileum, In Vitro Techniques, Ligands, Male, Mice, Muscle, Smooth, Neuralgia, Oligopeptides, Piperidines, Propionates, Radioligand Assay, Rats, Rats, Sprague-Dawley, Receptors, Opioid, delta, Receptors, Opioid, mu, Structure-Activity Relationship, Vas Deferens
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.

DOI10.1021/jm100982d
Alternate JournalJ. Med. Chem.
PubMed ID21128594
PubMed Central IDPMC3136578
Grant ListDA-06284 / DA / NIDA NIH HHS / United States
R01 DA013449-10 / DA / NIDA NIH HHS / United States
DA-13449 / DA / NIDA NIH HHS / United States
R01 DA013449 / DA / NIDA NIH HHS / United States
P01 DA006284 / DA / NIDA NIH HHS / United States
P01 DA006284-20 / DA / NIDA NIH HHS / United States
Faculty Member Reference: 
Yeon Sun Lee, Ph.D.
Frank Porreca, Ph.D.
Todd Vanderah, Ph.D.