Aromatic phosphonates inhibit the lysophospholipase D activity of autotaxin

Autotaxin (ATX), an extracellular lysophospholipase D, is a target for anticancer therapeutics We describe the synthesis of a set of α-substituted phosphonate analogs of the poorly bioavailable S32826, and we show the effects of shortening the chain and adding α-halo or α-hydroxy substituents on ATX inhibition. An optimal compound was identified for examination of biological effects of ATX inhibition.