Synthesis of D-myo-inositol 1,4,5-triphosphate analogues

Abstract

The cytosolic second messenger D-myo-inositol 1,4,5-trisphosphate (InsP₃), has the ability to mobilise Ca²⁺ from intracellular stores. Ca²⁺ controls a wide range of cellular processes, such as cell division and proliferation, apoptosis, fertilisation, gene transcription and muscle contraction. A number of potent InsP₃ receptor agonists are currently known; however, no selective InsP₃Rs antagonists have been reported to date. Using the X-ray crystal structure of the mouse type 1 InsP₃R, a range of analogues (below) has been designed with the intention of these compounds acting as competitive InsP₃Rs antagonists. The successful syntheses of these compounds are reported herein.