Synthesis and biological evaluation of l-α-Phosphatidyl-d-3-deoxy-3-heteromethyl-myo-inositols as phosphoinositide 3-kinase inhibitors Original Research Article

We have synthesized a series of 3-deoxy-3-heteromethyl derivatives of l-α-phosphatidyl-d-myo-inositol as part of our effort to develop specific, reversible inhibitors of phosphoinositide (PI) 3-kinase. Among various derivatives examined, phosphatidyl-d-3-deoxy-3-aminomethyl-myo-inositol displays the highest potency in inhibiting PI 3-kinase both in vitro and in cells. It effectively suppressed antigen-stimulated degranulation in mast cells (IC50, 17 μM), suggesting a potential application of this PI 3-kinase inhibitor as a mast cell-stabilizing agent.