The use of phosphate bioisosteres in medicinal chemistry and chemical biology

Abstract

Phosphate and pyrophosphate groups play a central role in cellular signalling and consequently are of great interest to both medicinal chemists and chemical biologists. However, the design of molecules that can interfere with phosphate-based processes is recognised as a significant challenge, especially when the resulting compounds must show good cellular penetration and stability. Herein, we have reviewed the full range of phosphate bioisosteres currently reported and provided the context of their deployment. We aim to provide a useful reference for medicinal chemists and chemical biologists who are engaged in the design of molecules that target phosphate-binding proteins.