Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1995-05-08
1997-12-30
Prior, Kimberly J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
552541, 552560, 552582, A61K 31575, C07J 900
Patent
active
057030677
ABSTRACT:
The present invention is directed to steroidal or terpenoidal compounds which inhibit farnesyl-protein transferase (FPTase). The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and treatment of cancer. The compounds of this invention have the following structure: ##STR1##
REFERENCES:
patent: 4871727 (1989-10-01), Burg et al.
patent: 4874755 (1989-10-01), Ashe et al.
patent: 5023250 (1991-06-01), Adams et al.
patent: 5141851 (1992-08-01), Brown et al.
patent: 5238922 (1993-08-01), Graham et al.
patent: 5245061 (1993-09-01), Singh
patent: 5260465 (1993-11-01), Singh et al.
patent: 5260479 (1993-11-01), Singh
patent: 5326773 (1994-07-01), Desolms et al.
patent: 5340828 (1994-08-01), Graham et al.
patent: 5352705 (1994-10-01), Deana et al.
De Bernardi, M., et al., "Fungal Metabolites XXIV*: Recent Chemical Investigations of Basidiomycetes Triterpenes and Their Biological Activities," Latinoamer. Quim vol. 20/2, pp. 57-64 (1989).
De Bernardi, M., et al., "Fungal Metabolites. IX. Triterpenes from Naematoloma Sublateritium," J. Nat. Products, vol. 44, pp. 351-356 (1981).
Gibbs, J.B., et al., "Selective Inhibition of Farnesyl-Protein Transferase Blocks Ras Processing in Vivo," The Jour. of Biol. Chem., vol. 268, No. 11, pp. 7617-7620 (1993).
Goldstein, J.L., et al., "Nonfarnesylated Tetrapeptide Inhibitors of Protein Farnesyltransferase," The Jour. of Biol. Chem., No. 24, pp. 15575-15578 (1991).
Ikeda, M., et al., "Isolation and Structure of Fasciculol A, a New Plant Growth Inhibitor from Neamatoloma fasciculare," Agric. Biol. Chem., vol. 41 (8), pp. 1539-1541 (1977).
James, G.L. et al., "Benzodiazepine Peptidomimetics: Potent Inhibitors of Ras Farnesylation in Animal Cells", Science, vol. 260, pp. 1937-1942 (1993).
Kikuchi, T., et al., "Syntheses of 24,25-Dideoxy-Fasciculol-A and Fasciculol-A, Constituent of Naematoloma Fasciculare (Fr.) Karst, A Poisonous Bitter Mushroom," Chem. Ltrs., pp. 1495-1498 (1979).
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 (1994).
Kohl, N.E. et al., "Selective Inhibition of ras-Dependent Transformation by a Farnesyltransferase Inhibitor", Science, vol. 260, pp. 1934-1937 (1993).
Kubo, I., et al., "Calmodulin Inhibitors from the Bitter Mushroom Naematoloma fasciculare (Fr.) Karst. (Strophariaceae) and Absolute Configuration of Fasciculols," Chem. Pharm Bull., vol. 33, pp. 3821-3825 (1985).
Pompliano, D.L., et al., "Steady-State Kinetic Mechanism of Ras Farnesyl: Protein Transferase", Biochemistry, vol. 31, pp. 3800-3807 (1992).
Qian, T., et al., "Design and Structural Requirements of Potent Peptidomimetic Inhibitors of p21 ras Farnesyltransferase", The Journal of Biol. Chem., vol. 269, No. 17, issue of Apr. 29, pp. 12410-12413 (1994).
Reiss, Y., "Inhibition of Purified p21ras Farnesyl:Protein Transferase by Cys-AAX Tetrapeptides", Cell, vol. 62, pp. 81-88 (1990).
Reiss, Y. et al., Sequence requirement for peptide recognition by rat brain p21 ras protein farnesyltransferase, (1991) Proc. Natl. Acad. Sci. USA, 88, pp. 732-736.
Ruzicka, L., et al., "Observations on Triterpenes (Part 96) Proof of the Identity of Lanosterol and Kryptosterol," Helv. Chim. Acta, vol. 28, 759, pp. 1-8 (1945).
Schaber, M.D., et al., "Polyisoprenylation of Ras in Vitro by a Farnesyl-Protein Transferase", The Journ. of Biol. Chem., vol. 365, No. 25, pp. 14701-14704 (1990).
Schulz, S. and Nyce, J.W., "Inhibition of protein farnesyltransferase: a possible mechanism of tumor prevention by dehydroepiandrosterone sulfate," Carcinogenesis, vol. 15, No. 11, pp. 2649-2652 (1994).
Simonsen, J. and Ross, W.C.J., "The Triterpenes and their Derivatives Hydrocarbons, Alcohols, Hydroxy-aldehydes, Ketones and Hydroxy-ketones," The Terprnes, vol. IV, pp. 39-115 (1957).
Singh, S.B., et al., "Fusidienol: A Novel Inhibitor of Ras Farnesyl-Protein Transferase from Fusidium griseum," Tetrahedron Letters, vol. 35, No. 27, pp. 4693-4696 (1994).
Suzuki, K., et al., "The Toxic Principles of Naematoloma Fasciculare," Chem. Pharm. Bull., vol. 31 (6) pp. 2176-2178 (1983).
Takahashi, A., et al., "Fasciculic Acids A, B and C as Calmodulin Antagonists from the Mushroom Naematoloma fasciculare," Chem. Pharm. Bull., vol. 37 (12) pp. 324703250 (1989).
Tinto, W.F. and John, L.M.D., "Triterpenoids of Jatropha Gossypiifolia," Jour. of Nat. Products, vol. 55, No. 6, pp. 807-809 (1992).
Tetrahedron, vol. 48, No. 33, pp. 6793-6798 (1992).
Steroids, vol. 53/3-5, pp. 579-596 (Mar.-May 1989).
Archives of Biochemistry and Biophysics, vol. 300, No. 2, Feb. 1, pp. 724-733 (1993).
Jayasuriya Hiranthi
Lingham Russell B.
Pelaez Fernando
Sanchez Manuel
Silverman Keith C.
Daniel Mark R.
Merck & Co. , Inc.
Muthard David A.
Prior Kimberly J.
LandOfFree
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.
Profile ID: LFUS-PAI-O-202389