Oxazole phosphonic acids as fructose 1,6-bisphosphatase inhibitors with potent glucose-lowering activity

To discover an alternative heterocyclic scaffold to the thiazole series of FBPase inhibitors such as thiazole 1, oxazoles were investigated to see if replacing the sulfur of the thiazole scaffold with an oxygen is tolerated. Numerous oxazoles with a phosphonic group linked by both 2,5-furandiyl and -COOCH(2)- groups were prepared and several oxazoles were discovered to have similar potency as thiazole 1. For example, oxazole 3.10 has an IC(50) of 70 nM and lowered blood glucose in normal fasted rats by 61%.