2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands

Bioorg Med Chem. 2006 Mar 15;14(6):2022-31. doi: 10.1016/j.bmc.2005.10.051. Epub 2005 Nov 15.

Abstract

A series of 2-benzyl and 2-phenyl-3-hydroxypropyl pivalates designed to incorporate the principal pharmacophores of phorbol esters have been synthesized and tested as PKC-alpha ligands. Among the analogues, 13c exhibited the most potent binding affinity with a Ki = 0.7 microM. The synthesized analogues were subjected to molecular modeling analysis based on two alternative models of the phorbol pharmacophore and a docking study of 13c was carried out.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Pentanoic Acids / chemical synthesis
  • Pentanoic Acids / chemistry*
  • Pentanoic Acids / metabolism
  • Phorbols / chemistry
  • Phorbols / metabolism
  • Protein Kinase C-alpha / chemistry*
  • Protein Kinase C-alpha / drug effects
  • Protein Kinase C-alpha / metabolism
  • Structure-Activity Relationship

Substances

  • Ligands
  • Pentanoic Acids
  • Phorbols
  • pivalic acid
  • Protein Kinase C-alpha