Synthesis and biological evaluation of new salvinorin A analogues incorporating natural amino acids

Bioorg Med Chem Lett. 2011 Jan 1;21(1):160-3. doi: 10.1016/j.bmcl.2010.11.046. Epub 2010 Nov 11.

Abstract

The synthesis and in vitro evaluation of a new series of salvinorin A analogues substituted at the C(2) position with natural amino acids is reported. Compound 12, containing Val, displayed high affinity and full agonist activity at the kappa-opioid receptor. Analogues with bulky and/or aromatic residues were inactive, showing the importance of size and electronegativity of C(2)-substituents for binding affinity of salvinorin A derivatives.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / chemistry*
  • Diterpenes, Clerodane / chemical synthesis*
  • Diterpenes, Clerodane / chemistry*
  • Diterpenes, Clerodane / pharmacology
  • Protein Binding
  • Receptors, Opioid, kappa / agonists
  • Receptors, Opioid, kappa / metabolism
  • Structure-Activity Relationship
  • Valine / analogs & derivatives*
  • Valine / chemical synthesis
  • Valine / chemistry
  • Valine / pharmacology

Substances

  • 2-(2'-amino-3-methylbutanoate)salvinorin B
  • Amino Acids
  • Diterpenes, Clerodane
  • Receptors, Opioid, kappa
  • Valine
  • salvinorin A