Semipeptoid farnesyl protein transferase inhibitors and analogs

Details Semipeptoid farnesyl protein transferase inhibitors and analogs Semipeptoid farnesyl protein transferase inhibitors and analogs

1996-09-03

1999-11-23

Celsa, Bennett

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

4 to 5 amino acid residues in defined sequence

530331, A61K 3807

Patent

active

059902779

ABSTRACT:
A farnesyl protein transferase (i.e., farnesyltransferase) inhibitors formed as peptoid and semipeptoid peptidomimetic compounds derived from a farnesyltransferase universal recognition tetrapeptide sequence CAAX (i.e., CAAX motif) and analogs thereof, and to the use of these compounds and analogs and ester derivatives thereof as chemotherapeutic agents in oncogenic or non-oncogenic Ras associated cancers and proliferative diseases.

REFERENCES:
patent: 5585359 (1996-12-01), Breslin et al.
patent: 5705686 (1998-01-01), Sebti et al.
Clerc, F. Et al, "Constrained Analogs Of KCVFM With Improved Inhibitopry Properties Against Farnesyl Transferase", Bioorganic & Medicinal Chem. Ltrs., vol. 5, No. 16, pp. 1779-1784 (1995).
Leftheris, K. Et al, "Peptide Based p21.sup.ras Farnesyl Transferase Inhibitors: Systematic Modification of the Tetrapeptide CA.sub.1 A.sub.2 X Motif", Bioorganic & Medicinal Chem. Ltrs., vol. 4, pp. 887-892 (1994).
Patel, D.V. et al, "Phosphinyl Acid-Based Bisubstrate Analop Inhibitors of Ras Farnesyl Protein Transferase", J. Med. Chem., vol. 38, No. 3, pp. 435-442 (1995).
Williams, T.M. et al, "2-Substituted Piperazines as Constrained Amino Acids, Application to the Synthesis of Potent, Non Carboxylic Acid Inhibitors of Farnesyltransferase", J. Med. Chem., vol. 39, No. 7, pp. 1345-1348 (1996).
Lerner, E. et al, "Disruption of Oncogenic K-Ras4B Processing and Signalling by a Potent Geranylgeranyltransferase I Inhibitor", J. Biol. Chem., vol. 270, No. 45, pp. 26770-26773 (1995).
Cox, A.D. et al, "The CAAX Peptidomimetic Compound B581 Specifically Blocks Farnesylated, But Not Geranylgeranylated or Myristylated, Oncogenic Ras Signaling and Transformation", J. Biol. Chem. , vol. 269, No. 30, pp. 19203-10206 (1994).
Graham, S.L. et al. "Pseudopeptide Inhibitors of Ras Farnesyl-Protein Transferase", J. Med Chem., vol. 37, No. 6, pp. 725-732 (1994).
Kohl, N.E. et al, "Selective Inhibition of ras-Dependent Transformation by a Farnesyltransferase Inhibitor" Science, Vil. 260, pp. 1934-1936 (Jun. 1993).
James, G.L. et al, "Benzodiazepine Peptidomimetics: Potent Inhibitors of Ras Farneslation in Animal Cells", Science, vol. 260, pp. 1937-1942 (Jun. 1993).
Hancock, J.F., "Anti-Ras Drugs Come of Age", Current Biology, vol.3, No. 11, pp. 770-772 (1993).
Gibbs, J.B. et al, "Farnesyltransferase Inhibitors: Ras Research Yields a Potential Cancer Therapeutic", Cellvol. 77, pp. 175-178 (Apr. 1994).
Manne, V. Et al, "Bisubstrate Inhibitors of Farnesyltransferase: A Novel Class of Specific Inhibitors of Ras Transformed Cells", Oncogene, vol. 10, pp. 1763-1779 (1995).
Vogt, A. Et al, "A Non-Peptide Mimetic of Ras-CAAX: Selective Inhibition of Farnesyltransferase and Ras Processing", J. Biol. Chem., vol. 270, No. 2, pp. 660-664 (1995).
Byk, G. Et al, "Local Constrained Shifty Pseudopeptides Inhibitors of Ras-Farnesyl Transferase" Bioorganic & Medical Letters, vol. 5, No. 22, pp. 2677-2682 (1995).
Kohl, N.E. et al, "Inhibition of Farnesyltransferase Induces Regression of Mammary and Salivary Carcinomas in ras Transgenic Mice", Nature Medicine, vol. 1, No. 8, pp. 792-797 (1995).
Kohl, N.E. et al, "Protein Farnesyltransferase Inhibitors Block the Growth of ras-Dependent Tumors in Nude Mice", Proc. Nat. Acad. Sci. USA, vol. 91 pp. 9141-9145 (1994).
Leftheris, K. Et al, "Development of Highly Potent Inhibitors of Ras Farnesyltransferase Possessing Cellular and in vitro Activity", J. Med Chem., vol. 39, pp. 224-236 (1996).
Brown, M. S. Et al, "Tetrapeptide Inhibitors of Protein Farnesyltransferase: Amino-Terminal Substitution in Phenylalanine-Containing Tetrapeptides Restores Farnesylation", Proc. Nat. Acad. Sci. USA, vol. 89, pp. 8313-8316 (1992).
Kato, K. Et al, "Isoprenoid Addition to Ras Protein is the Critical Modification for its Membrane Association and Transforming Activity", Proc. Nat. Acad. Sci. USA, vol. 89, pp. 6403-6407 (1992).
Hancock, J.F. et al, "All ras Proteins are Polyisoprenylated But only Some aare Palmitoylated", Cell, vol. 57, pp. 1167-1177 (1989).
Goldstein, J.L. et al, "Nonfarnesylated Tetrapeptide Inhibitors of Protein Farnesyltransferase", J. Biol. Chem., vol. 266, No. 24, pp. 15575-15578 (1991).
Zuckermann, R.N. et al, "Efficient Method for the Preparation of Peptoids [Oligo (N-substituted glycines)] by Submonomer Solid-Phase Synthesis", J. Am. Chem. Soc., vol. 114, pp. 10646-10647 ((1992).
Zuckermann, R.N. et al, "Discovery of Nanomolar Ligands for 7--Transmembrane G-Protein-Coupled Receptors from a Diverse N-(Substituted) Glycine Peptoid Library", J. Med. Chem., vol. 37, pp. 2678-2685 (1994).
Kessler, H., "Peptides -A New Approach to the Development of Pharmaceuticals", Angew. Chem. Int. Ed. Engl., vol. 32, No. 4, pp. 543-544 (1993).
Simon, R.J. et al, "Peptoids: A Modular Approach to Drug Discovery", Proc. Nat. Acad. Sci. USA, vol. 89, pp. 9367-9371 (1992).
Miller, S.M. et al, "Comparison of the Proteolytic Susceptibilities of Homologous L-Amino Acid, and N-Substituted Glycine Peptide and Peptide Oligomers", Drug Development Research, vol. 35, No. 20, pp. 20-32 (1995).
Moores, S.L. et al, "Sequence dependence of Protein Isoprenylation", J. Biol. Chem., vol. 266, No. 22, pp. 14603-14610, (1991).
Miller, S.M. et al, "Proteolytic Studies of Homologous Peptide and N-Substituted Glycine Peptide and Peptide Oligomers", Bioorg. & Med. Chem. Ltrs., vol. 4, No. 22, pp. 2657-2662 (1994).
Gallop, M.A. et al, "Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries", J. Med. Chem., vol. 37, No. 9, pp. 1233-1251 (1994).
Gibbs, J.B., "Ras C-Terminus Processing Enzymes---New Drug Targets?" Cell, vol. 65, pp. 1-4 (1991).
Reiss, Y. et al, "Sequence requirement for Peptide Recognition by Rat Brain p21.sup.ras Protein Farnesyltransferase", Proc. Natl. Acad. Sci. USA, vol. 88, pp. 732-736 (1991).
Houghten, R.A., "General Method for the Rapid Solid-Phase Synthesis of Large Numbers of Peptides: Specificity of Antigen-Antibody Interaction at the Level of Individual Amino Acids", Proc. Natl. Acad. Sci. USA, vol. 82, pp. 5131-5135 (1985).
deSolms, S. J. et al, "Pseudopeptide Inhibitors of Protein Farneslytransferase", J. Med. Chem., vol. 38, pp. 3967-3971 (1995).
Garcia, A.M. et al, "Peptidomimetic Inhibitors of Ras Farnesylation and Function in Whole Cells", J. Biol. Chem., vol. 268, No. 25, pp. 18415-18418 (1993).
Reiss, Y. Et al, "Inhibition of Purified p21.sup.ras Farnesyl: Protein Transferase by Cys-AAX Tetrapeptides", Cell, vol. 62, pp. 81-88, (1990).
Kruijtzer, J.A. et al, "Synthesis in Solution of Peptoids using Fmoc-Protected N-Substituted Glycines", Tetrahedron Letters, vol. 36, No. 38, pp. 6969-6972 (1995).
Bodor, N. et al, "A Strategy for Delivering Peptides into the Central Nervous System by Sequential Metabolism", Science, vo. 257, pp. 1698-1700 (1992).
Maltese, W.A., "Posttranslational Modification of Proteins by Isoprenoids in Mammalian Cells", FASEB Journal, vol. 4, pp. 3319-3328, (1990).

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