Abstract
Enkephalin analogues with a 4-anilidopiperidine scaffold have been designed and synthesized to achieve therapeutic benefit for the treatment of pain due to mixed mu and delta opioid agonist activities. Ligand 16, in which a Dmt-substituted enkephalin-like structure was linked to the N-phenyl-N-piperidin-4-yl propionamide moiety, showed very high binding affinities (0.4 nM) at mu and delta receptors with an increased hydrophobicity (aLogP = 2.96). This novel lead compound was found to have very potent agonist activities in MVD (1.8 nM) and GPI (8.5 nM) assays.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Binding, Competitive
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Cell Line
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Cricetinae
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Cricetulus
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Enkephalins / chemical synthesis*
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Enkephalins / pharmacology
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Guinea Pigs
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Humans
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Ileum / drug effects
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Ileum / physiology
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In Vitro Techniques
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Male
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Mice
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Radioligand Assay
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Rats
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Receptors, Opioid, delta / agonists*
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Receptors, Opioid, mu / agonists*
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Structure-Activity Relationship
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Vas Deferens / drug effects
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Vas Deferens / physiology
Substances
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Enkephalins
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Receptors, Opioid, delta
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Receptors, Opioid, mu