title: Synthesis and biological evaluation of L-alpha-phosphatidyl-D-3-deoxy-3-heteromethyl-myo-inositols as phosphoinositide 3-kinase inhibitors.
abstract: We have synthesized a series of 3-deoxy-3-heteromethyl derivatives of L-alpha-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 (IC(50), 17 microM), suggesting a potential application of this PI 3-kinase inhibitor as a mast cell-stabilizing agent.
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Wang
authors.forename: C S
authors.initials: CS
authors.lastname: Chen
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001671:Biochemistry / Q000379:methods; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007294:Inositol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D013329:Structure-Activity Relationship; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C448862:phosphatidyl-3-deoxy-3-aminoethyl-inositol; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007294:Inositol; D000077191:Wortmannin