Inhibitors of phosphatidyl myo-inositol cycle

Details Inhibitors of phosphatidyl myo-inositol cycle Inhibitors of phosphatidyl myo-inositol cycle

2006-12-26

2006-12-26

Zucker, Paul A. (Department: 1621)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Phosphorus containing other than solely as part of an...

C558S276000, C560S182000

Reexamination Certificate

active

07153843

ABSTRACT:
The present invention relates to the preparation and biological activity of 3-deoxy-Dmyo-inositol ether lipid analogs as inhibitors of phosphatidylinositol-3-kinase signaling and cancer cell growth. The compounds of the present invention are useful as anti-tumor 5 agents which effectively inhibit the growth of mammalian cells.

REFERENCES:
Hu et al, Molecular and Cellular Biology, Interaction of Phosphotidylinositol 3-Kinase-Associated p85 with Epidermal Growth Factor and Platelet-Derived Growth Factor Receptors, 1992, pp. 981-990.
J Med Chem 43, pp. 3045-3051 by Hu et al Jul. 2000.
Carpenter et al., J. Biol. Chem., “Phosphoinositide 3-Kinase is Activated by Phosphopeptides that Bind to the SH2 Domains of the 85kDa Subunit,” 268: 9478-9483 (1993).
Kozikowski et al., J. of Medical Chem., “Synthesis and Biology of 1D-3-Deoxyphosphatidylinositol: A Putative Antimetabolite of Phosphatidylinositol-3-Phosphate and an Inhibitor of Cancer Cell Colony Formation,” 38: 1053-1056 (1995).
Hu et al., Bioorganic & Medicinal Chemistry Letters 11(2001 173-176, “3-Deoxy-3substituted-d-myo-inositol Imidazolyl Ehter Lipid Phosphates and Carbonate as Inhibitors of the Phosphatidylinositol 3-Kinase Pathway and Cancer Celll Growth”.
Kozikowski, et al., Teirahedron, “Synthesis of 1D-3-Deoxy- and -2,3-Dideoxyphosphatidylinositol”, vol. 53, No. 44, pp. 14903-14914, 1997.
Schultz et al., Anticancer Res., “In Vitro and In Vivo Antitumor Activity of the Phosphatidylinositol-3-Kinase Inhibitor, Wortmannin,” 15: 1135-1140 (1995). Abstract.
Wymann et al., Mol. Cell Biol., “Wortmannin Inactivates Phosphoinositide 3-Kinase by Covalent Modification of Lys-802, a Residue Involved in the Phosphate Transfer Reaction” 16:1722-1733 (1996).
Cross et al., J. Biol. Chem, “Wortmannin and its structural analogue demethoxyvirdin inhibit stimulated phospholipase A2 activity in swiss 3T3 cells Wortmannin is not a specific inhibitor orf phosphatidylinositol 3-kinase” 270: 25352-25355 (1995).
Lemmon et al., Cell, “PH domains: diverse sequences with a common fold recruit signaling molecules to the cell surface” 85: 621-624 (1996). Abstract.
Nakanishi et al., J. Biol Chem, “Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphospate” 268: 13-6 (1993).

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