Synthesis and protein kinase C inhibitory activities of balanol analogs with replacement of the perhydroazepine moiety

J Med Chem. 1997 Jan 17;40(2):226-35. doi: 10.1021/jm960497g.

Abstract

Balanol is a potent protein kinase C (PKC) inhibitor that is structurally composed of a benzophenone diacid, a 4-hydroxybenzamide, and a perhydroazepine ring. A number of balanol analogs in which the perhydroazepine moiety is replaced have been synthesized and their biological activities evaluated against both PKC and cAMP-dependent kinase (PKA). The results suggested that the activity and the isozyme/kinase selectivity of these compounds are largely related to the conformation about this nonaromatic structural element of the molecules.

MeSH terms

  • Azepines / chemical synthesis*
  • Azepines / pharmacology*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Hydroxybenzoates / chemical synthesis*
  • Hydroxybenzoates / pharmacology*
  • Isoenzymes / antagonists & inhibitors*
  • Molecular Conformation
  • Protein Kinase C / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Azepines
  • Enzyme Inhibitors
  • Hydroxybenzoates
  • Isoenzymes
  • ophiocordin
  • Protein Kinase C