Synthesis of (+/-)-2-O-[4'-(N-9''-purinyl)butyl] myo-inositol 1,4,5-tris(phosphate), a potent full agonist at the D-myo-inositol 1,4,5-tris(phosphate) receptor

J Med Chem. 2005 Feb 24;48(4):1251-5. doi: 10.1021/jm049458s.

Abstract

Racemic 2-O-[4'(9''-N-purinyl)butyl] myo-inositol 1,4,5-tris(phosphate) 8 was synthesized starting from myo-inositol. Substitution of position 2 by an alkyl side chain was rendered possible by inversion of the chair conformation of the inositol ring by means of an orthoester. The final compound is a full agonist with the same order of potency as d-myo-inositol 1,4,5-tris(phosphate).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / ultrastructure
  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Cattle
  • Cell Line
  • Endoplasmic Reticulum / metabolism
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate / analogs & derivatives*
  • Inositol 1,4,5-Trisphosphate / chemical synthesis*
  • Inositol 1,4,5-Trisphosphate / chemistry
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Inositol 1,4,5-Trisphosphate Receptors
  • Microsomes / drug effects
  • Microsomes / metabolism
  • Molecular Conformation
  • Pancreas / cytology
  • Permeability
  • Purines / chemical synthesis*
  • Purines / chemistry
  • Purines / pharmacology
  • Radioligand Assay
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Stereoisomerism

Substances

  • 2-O-(4'-(N-9''-purinyl)butyl) myo-inositol 1,4,5-tris(phosphate)
  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Purines
  • Receptors, Cytoplasmic and Nuclear
  • Inositol 1,4,5-Trisphosphate
  • Calcium