Synthesis and biological evaluation of L-alpha-phosphatidyl-D-3-deoxy-3-heteromethyl-myo-inositols as phosphoinositide 3-kinase inhibitors

We have synthesized a series of 3-deoxy-3-heteromethyl derivatives of L-alp ha -phosphatidly-D-myo-inositol as part of our effort to develop specific, reversible inhibitors of phosphoinositide (PI) 3-kinase. Among various deri vatives examined. phosphatidyl-D-3-deoxy-3-aminomethyl-myo-inositol display 's 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 muM), suggesting a potential application of this PI 3-kinase inhi bitor as a mast cell-stabilizing agent. (C) 2001 Elsevier Science Ltd. All rights reserved.