Development of Potent μ and δ Opioid Agonists with High Lipophilicity
| Autor: | Katherine E. Hanlon, Frank Porreca, Victor J. Hruby, Vinod Kulkarani, Ruben Vardanyan, Shou Wu Ma, Scott Cowell, Peg Davis, Todd W. Vanderah, Yeon Sun Lee, Josephine Lai |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Cell Membrane Permeability Stereochemistry Receptors Opioid mu CHO Cells In Vitro Techniques Ligands Binding Competitive Article Rats Sprague-Dawley Mice Radioligand Assay Structure-Activity Relationship Cricetulus Vas Deferens Piperidines Ileum In vivo Cricetinae Receptors Opioid delta Drug Discovery medicine Animals Humans Structure–activity relationship Moiety Tetrapeptide Chemistry Ligand Halogenation Muscle Smooth Amides Rats Analgesics Opioid Opioid Hyperalgesia Lipophilicity Neuralgia Molecular Medicine Propionates Oligopeptides medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 54:382-386 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm100982d |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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