Inhibitors of farnesyl-protein transferase

Details Inhibitors of farnesyl-protein transferase Inhibitors of farnesyl-protein transferase

1994-04-04

1995-05-30

Prescott, Arthur C.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acid esters

560179, 560183, A61K 3166, A61K 3112, A61K 3122, A61K 3144

Patent

active

054203341

ABSTRACT:
The present invention is directed to compounds which inhibit farnesyl-protein transferase (FPTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting famesyl-protein transferase and the famesylation of the oncogene protein Ras.

REFERENCES:
patent: 5043268 (1991-08-01), Stock
patent: 5141851 (1992-08-01), Brown et al.
patent: 5238922 (1993-08-01), Graham et al.
patent: 5245061 (1993-09-01), Singh
patent: 5256399 (1993-10-01), Sessler et al.
patent: 5260465 (1993-11-01), Singh et al.
patent: 5260479 (1993-11-01), Singh
patent: 5276217 (1994-01-01), Tius
patent: 5294627 (1994-03-01), Arison et al.
patent: 5326773 (1994-07-01), de Solms et al.
patent: 5340828 (1994-08-01), Graham et al.
patent: 5350867 (1994-09-01), Singh
patent: 5352705 (1994-10-01), Deana et al.
Kohl, N. E. et al., "Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice", Proc. Natl. Acad. Sci. USA, vol. 91, pp. 9141-9145 (Feb. 1994).
Aldridge, D. C. et al., Metabolites of Nectria coccinea, (Mar. 1972), J. C. S. Perkin I, pp. 2136-2141.
Bos, J. L., ras Oncogenes in Human Cancer: A Review (Apr.1989), Cancer Research, 49, pp. 4682-4689.
Carey, S. T. and Nair, M. S. R. Metabolites from Pyrenomycetes VIII. Identification of Three Metabolites from Nectria Lucida as Antibiotic Triprenyl Phenols, (1977), The Journal of Natural Products, 40, No. 6, pp. 519-642.
Ellestad, G. A. et al., Some New Terpenoid Metabolites From An Unidentified Fusarium Species, (Feb. 1969), Tetrahedron, 25, pp. 1323-1334.
Gibbs, J. B. et al., Selective Inhibition of Farnesyl-Protein Transferase Blocks Ras Processing in Vivo, (Sep. 1993), The Journal of Biol. Chemistry, 268, No. 11, pp. 7617-7620.
Gibbs, J. B., Ras C-Terminal Processing Enzymes-New Drug Targets?, (Jun. 1991), Cell, 65, 1-4, pp. 1-4.
Goldstein, J. S., et al. Journal of Biological Chemistry, vol. 266, No. 24, pp. 15575-15578 (Jul. 1991).
James, G. L. et al., Benzodiazepine Peptidomimetics: Potent Inhibitors of Ras Farnesylation in Animal Cells, (Sep. 1993), Science, 260, pp. 1937-1942.
Kawagishi, H. et al., Isolation and Structure of a New Diprenyl Phenol, Colletorin B Produced by Cephalosporium diospyri, (Jul. 1984), Agric. Biol. Chem., 48 (7), pp. 1903-1904.
Kohl, N. E. et al., Selective Inhibition of ras-Dependent Transformation by a Farnesyltransferase Inhibitor, (Sep. 1993), Science, 260, pp. 1934-1937.
Leftheris, K. et al., Peptide Based P21RAS Farnesyl Transferase Inhibitors: Systematic Modification of the Tetrapeptide CA1A2X Motif, (Nov. 1994), Bioorganic & Medicinal Chemistry Letters, 4, No. 7, pp. 887-892.
Pompliano, D. L. et al., Steady-State Kinetic Mechanism of Ras Farnesyl:Protein Transferase, (Oct. 1992), Biochemistry, 31, pp. 3800-3807.
Qian, Y. et al., Design and Structural Requirements of Potent Peptidomimetic Inhibitors of p21ras Farnesyltransferase, (Nov. 1994), The Journal of Biological Chemistry, 269, No. 17, pp. 12410-12413.
Reiss, Y. et al., Inhibition of Purified p21ras Farnesyl:Protein Transferase by Cys-AAX Tetrapeptides, (Aug. 1990), Cell, 62, pp. 81-88.
Reiss, Y. et al., Sequence requirement for peptide recognition by rat brain p21 ras protein farnesyltransferase, (Jun. 1991), Proc. Natl. Acad. Sci. USA, 88, pp. 732-736.
Sasaki, H. et al., Isolation and Structure of Ascochlorin and Its Analogs, (Feb. 1974), Agr. Biol. Chem., 38 (8), pp. 1463-1466.
Schaber, M. D. et al., Polyisoprenylation of Ras in Vitro by a Farnesyl-Protein Transferase, (Jan. 1990), The Journal of Biological Chemistry, 265, No. 25, pp. 14701-14704.

Affiliated with

Also associated with

Rating

Inhibitors of farnesyl-protein transferase 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 farnesyl-protein transferase, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Inhibitors of farnesyl-protein transferase will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-363617