Novel bisphosphonate inhibitors of phosphoglycerate kinase

A series of novel, conformationally-restrained bisphosphonate analogues of 1,3-bisphosphoglyceric acid 1 have been synthesised and evaluated as inhibitors of 3-PGK. They are competitive inhibitors of the human enzyme and, especially for certain α-halophosphonic acid analogues, both Ki and IC50 values extend into the submicromolar range.