Inhibitors of human phosphatidyl-inositol 3-kinase delta

Details Inhibitors of human phosphatidyl-inositol 3-kinase delta Inhibitors of human phosphatidyl-inositol 3-kinase delta

2005-09-27

2005-09-27

Raymond, Richard L. (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C514S266100, C514S266200, C514S266230, C514S266300, C544S264000, C544S265000, C544S283000, C544S287000, C544S290000, C544S319000

Reexamination Certificate

active

06949535

ABSTRACT:
Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3Kδ) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3Kδ plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3Kδ, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3Kδ activity, including compounds that selectively inhibit PI3Kδ activity. Methods of using PI3Kδ inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3Kδ inhibitory compounds to inhibit PI3Kδ-mediated processes in vitro and in vivo.

REFERENCES:
patent: 3322756 (1967-05-01), Ruschig et al.
patent: 3984555 (1976-10-01), Amschler et al.
patent: 4183931 (1980-01-01), Wolfe et al.
patent: 4225489 (1980-09-01), Rolf et al.
patent: 5378725 (1995-01-01), Bonjouklian et al.
patent: 5480906 (1996-01-01), Creemer et al.
patent: 5858753 (1999-01-01), Chantry et al.
patent: 6046049 (2000-04-01), Monia et al.
patent: 0 675 124 (1995-04-01), None
patent: 0 884 310 (1998-12-01), None
patent: 0 900 568 (1999-03-01), None
patent: 1356763 (1974-12-01), None
patent: 55 118918 (1980-09-01), None
patent: 55 118917 (1980-12-01), None
patent: 56 2322 (1981-01-01), None
patent: WO 94/17090 (1994-04-01), None
patent: 9524379 (1995-09-01), None
patent: WO 96/04923 (1996-02-01), None
patent: WO 96/25488 (1996-08-01), None
patent: WO 97/41097 (1997-11-01), None
patent: WO 97/46688 (1997-12-01), None
patent: WO 98/33802 (1998-08-01), None
patent: WO 99/08501 (1999-02-01), None
patent: WO 99/34804 (1999-07-01), None
patent: WO 01/00881 (2001-01-01), None
patent: WO 01/81346 (2001-05-01), None
patent: WO 01/53266 (2001-07-01), None
patent: WO 01/57034 (2001-08-01), None
patent: WO 01/30768 (2001-11-01), None
Y-T. Chang et al., “Inositol phospholipid pathway inhibitors and regulators,”Exp. Opin. Ther. Patents, 11, (1) pp. 45-59 (2001).
Computer Search (8 pages).
J. Downward, “A target for PI(3) kinase,”Nature, 376, pp. 553-554 (1995).
S. Volinia et al., “Molecular cloning, cDNA sequence, and chromosomal localization of the human phosphatidylinositol 3-kinase p110α (PIK3CA) gene,”Genomics, 24, pp. 472-477 (1994).
B. Vanhaesebroeck et al., “A novel human phosphoinositide 3-kinase,”FASEB Journal, 10, p. A1395 (1996).
Boudewijn et al., “Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction,”Nature, 376, pp. 599-602 (1995).
Eichholtz et al., “A myristoylated pseudosubstrate peptide, a novel protein kinase C inhibitor,”J. Biol. Chem., 268, pp. 1982-1986 (1993).
Hiles et al., “Phosphatidylinositol 3-kinase: Structure and expression of the 100 kd catalytic subunit,”Cell, 70, pp. 419-429 (1992).
Hu et al., “Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85,”Mol. Cell. Biol., 13, pp. 7677-7688 (1993).
Hu et al., “Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase,”Science, 268, pp. 100-102 (1995).
T. Hunter, “When is a lipid kinase not a lipid kinase? When it is a protein kinase,”Cell, 83, pp. 1-4 (1995).
Otsu et al., “Characterization of two 85 kd proteins that associate with receptor tyrosine kinases, middle-T/pp60c-STCcomplexes, and PI3-kinase,”Cell, 65, pp. 91-104 (1991).
Pages et al., “Binding of phosphatidyl-inositol-D-OH kinase to CD28 is required for T-cell signalling,”Nature, 369, pp. 327-329 (1994).
Panayotou et al., “Phosphatidyl-inositol 3-kinase: A key enzyme in diverse signalling processes,”Trends in Cell Biol., 2, pp. 358-360 (1992).
P.J. Parker, “PI 3-kinase puts GTP on the Rac,”Current Biology, 5, pp. 577-579 (1995).
Rameh et al., “Phosphatidylinositol (3,4,5)P3interacts with SH2 domains and modulates PI 3-kinase associate with tyrosine-phosphorylated proteins,”Cell, 83, pp. 821-830 (1995).
Rodriguez-Viciana et al., “Activation of phosphoinositide 3-kinase by interaction ewith ras and by point mutation,”EMBO Journal., 15, pp. 2442-2451 (1996).
C.E. Rudd, “Upstream-downstream” CD28 cosignaling pathways and T cell function,Immunity, 4, pp. 527-534 (1996).
Stephens et al., “Characterization of a phosphatidylinositol-specific phosphoinositide 3-kinase from mammalian cells,”Current Biology, 4, pp. 203-214 (1994).
Stoyanov et al., “Cloning and characterization of a G protein-activated human phosphoinositied-3 kinase,”Science, 269, pp. 690-693 (1995).
Thelan et al., “Wortmannin binds specifically to 1-phosphatidylinositol 3-kinase while inhibiting guanine nucleotide-binding protein-coupled receptor signaling in neutrophil leukocytes,”Proc. Natl. Acad. Sci. USA., 91, pp. 4960-4964 (1994).
Volinia et al., “Chromosomal localization of human p85α, a subunit of phosphatidylinositol 3-kinase, and its homologous p85β,”Oncogene, 7, pp. 789-793 (1992).
Yao et al., “Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor,”Science, 267, pp. 2003-2006 (1995).
D. Chantry et al, “p110δ, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes,”J. Biological Chemistry, 272(31), pp. 19236-19241 (1997).
Genbank Accession No. U57843, “Human phosphatidylinositol 3-kinase delta catalytic subunit mRNA,” deposited by A.J. Morris, dated May 10, 1997.
B. Vanhaesebroeck et al., “p110δ, a novel phosphoinositide 3-kinase in leukocytes,”Proc. Natl. Acad. Sci., USA, 94, pp. 4330-4335 (1997).
S. Volinia et al., “A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system,”EMBO J., 14(14), pp. 3339-3348 (1995).
Carnero et al., Wortmannin, an inhibitor of phosphatidyl-inositol 3-kinase, induces oocyte maturation through a MPF-MAPK-dependent pathway,FEB Letters, 422, pp. 155-159 (1998).
Ager et al., “Synthesis and central Nervous system activity of quinazolinones methaqualone,” J. Medicinal Chem., 20/3, 379-86 (1977).
CAS Abstract DN 86:83505-1977:83505, pp. 111-118.
T.L. Rathman et al., American Chemical Society, 45, pp. 2169-2176 (1980).
Ismail et al., Chemical Abstracts, vol. 98, No. 1, p. 406 (1983).
Parasharya et al., Chemical Abstracts, vol. 121, No. 9, p. 1065 (1994).
Barakat et al., Chemical Abstracts, vol. 124, No. 21, p. 1334 (1996).
Chern et al., Chemical Abstracts, vol. 129, No. 16, p. 676 (1998).
El-Feky et al., Chemical Abstracts, vol. 131, No. 23, p. 497 (1999).
El-Feky et al., Chemical Abstracts, vol. 106, No. 13, p. 650 (1987).
M.F. Hassan et al., Chinese Journal of Chemistry, vol. 9, No. 3, pp. 262-269 (1991).
Chemical Abstract 106:102196.

Affiliated with

Also associated with

Rating

Inhibitors of human phosphatidyl-inositol 3-kinase delta does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Inhibitors of human phosphatidyl-inositol 3-kinase delta, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Inhibitors of human phosphatidyl-inositol 3-kinase delta will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3403929