Aminothiazolomorphinans with mixed κ and μ opioid activity.

Abstract

A series of N-substituted and N'-substituted aminothiazole-derived morphinans (5) were synthesized for expanding the structure-activity relationships of aminothiazolo-morphinans. Although their affinities were somewhat lower than their prototype aminothiazolo-N-cyclopropylmorphinan (3), 3-aminothiazole derivatives of cyclorphan (1) containing a primary amino group displayed high affinity and selectivity at the κ and μ opioid receptors. [(35)S]GTPγS binding assays showed that the aminothiazolomorphinans were κ agonists with mixed agonist and antagonist activity at the μ opioid receptor. These novel N'-monosubstituted aminothiazole-derived morphinans may be valuable for the development of drug abuse medications.

• Authors: Tangzhi Zhang, Zhaohua Yan, Anna Sromek, Brian I Knapp, Thomas Scrimale, Jean M Bidlack, John L Neumeyer
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 54 Issue 6 Pg. 1903-13 (Mar 24 2011) ISSN: 1520-4804 [Electronic] United States
• PMID: 21351746 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Morphinans
• Receptors, Opioid, kappa
• Receptors, Opioid, mu
• Thiazoles

Topics

• Animals
• CHO Cells
• Cricetinae
• Cricetulus
• Humans
• Morphinans (chemical synthesis, chemistry, pharmacology)
• Radioligand Assay
• Receptors, Opioid, kappa (agonists)
• Receptors, Opioid, mu (agonists, antagonists & inhibitors)
• Stereoisomerism
• Structure-Activity Relationship
• Thiazoles (chemical synthesis, chemistry, pharmacology)