Geranylgeranyl pyrophosphate synthase inhibitors

Details Geranylgeranyl pyrophosphate synthase inhibitors Geranylgeranyl pyrophosphate synthase inhibitors

2007-09-11

2007-09-11

Page, Thurman K. (Department: 1621)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

C514S102000, C514S090000, C514S091000, C544S057000, C544S157000, C546S022000, C548S413000

Reexamination Certificate

active

11212128

ABSTRACT:
The invention provides novel pyrophosphate synthase inhibitors of formula I as well as compositions comprising such inhibitors and methods for their use.

REFERENCES:
patent: 4559157 (1985-12-01), Smith et al.
patent: 4608392 (1986-08-01), Jacquet et al.
patent: 4774262 (1988-09-01), Blanquet et al.
patent: 4820508 (1989-04-01), Wortzman et al.
patent: 4938949 (1990-07-01), Borch et al.
patent: 4992478 (1991-02-01), Geria et al.
patent: 5583122 (1996-12-01), Benedict et al.
patent: 6727234 (2004-04-01), Wiemer et al.
patent: 2004/0167102 (2004-08-01), Wiemer et al.
Cohen et al., Inhibition of human smooth muscle cell proliferation in culture by farnesyl pyrophosphate analogues, inhibitors of in vitro protein: farnesyl transferase, Biochemical Pharmacology, vol. 57, pp. 365-373, 1999.
Muehlbauer et al., Effect of various Polyphosphonates on ectopic Calcification and Bone Resorption in Rats, Mineral and Electrolyte Metabolism, 1981, 5 (6), 296-303.
Cohen et al., {Inhibition of human smooth muscle cell proliferation in culture by farnesyl pyrophosphate analogues, inhibitors of in vitro protein: farnesyl transferase, Biochemical Pharmacology, vol. 57, pp. 365-373, 1999}.
Muehlbauer et al., {Effect of various Polyphosphonates on ectopic Calcification and Bone Resorption in Rats, Mineral and Electrolyte Metabolism, 1981, 5 (6), 296-303}.
Cohen, L. H. et al., “Inhibition of human smooth muscle cell proliferation in culture by farnesyl pyrophosphate analogues, inhibitors of in vitro protein: Farnesyl transferase”Biochemical Pharmacology,vol. 57, No. 4, 365-474, 1999.
Fairlamb, I J S et al., “Cycloisomerisation of modified terpenoid 1,6-enynes-synthesis of conformationally-restricted cyclic farnesyl analogues”,Tetrahedron Letters, vol. 43, No. 30, 5327-5331, 2002.
Hutchinson, D. W. et al., “Synthesis of alkylated methylene bisphosphonates via organothallium intermediates”,Journal of Organometallic Chemistry, vol. 291, No. 2, 145-151, 1985.
Muehlbauer, R. C. et al., “Effect of various polyphosphonates on ectopic calcification and bone resorption in rats”,Mineral and Electrolyte Metabolism,vol. 5, No. 6, 296-303, 1981.
Quimby, O. T. et al., “Metalated methylenediphosphate esters. Preparation characterisation and synthetic applications”,Journal of Organometallic Chemistry,vol. 291, No. 2, 145-151, 1968.
Valentijn, A. R. P. M. et al., “Synthesis of Pyrophosphonic Acid Analogues of Farnesyl Pyrophosphate”,Tetrahedron, vol. 51, No. 7, 2099-2108, 1995.
International PCT Search Report for PCT/US2005/030304, (2006).
Armstrong et al. “cDNA cloning and expression of the alpha and beta subunits of rat Rab geranylgeranyl transferase.”J. Biol. Chem.268: 12221—12229 (1993)
Benford et al. “Farnesol and geranylgeraniol prevent activation of caspases by aminobisphosphonates: biochemical evidence for two distinct pharmacological classes of bisphosphonate drugs.”Mol Pharmacol.56(1):131-140 (1999).
Bergstrom et al. “Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase.”Arch Biochem Biophys.373(1):231-241 (2000).
Ebetino et al. “Recent Work on the Synthesis of Phosphonate-containing, Bone-active Heterocyles”Heterocycles30:855-862 (1990).
Ericsson et al. “Distribution of prenyltransferases in rat tissues,”J. Biol. Chem.268: 832-838 (1993).
Ericsson et al. “Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression.”J. Lipid Res.39(9):1731-1739 (1998).
Fisher et al. “Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro.”PNAS,96(1):133-138 (1999).
Fuse et al. “Regulation of geranylgeranyl pyrophosphate synthase in the proliferation of rat FRTL-5 cells: involvement of both cAMP-PKA and PI3-AKT pathways,”Biochem Biophys Res Commun.315(4):1147-1153 (2004).
Holstein et al. “Consequences of Mevalonate Depletion.”J. Biol. Chem.277:10678-10682 (2002).
Holstein et al. “Isoprenoid pyrophosphate analogues regulate expression of Ras-related proteins.”Biochemistry42(15): 4384-4391 (2003).
Holstein et al. “Isoprenoids influence expression of Ras and Ras-related proteins.”Biochemistry41:13698-13704 (2002).
Holstein et al. “Phosphonate and bisphosphonate analogues of farnesyl pyrophosphate as potential inhibitors of farnesyl protein transferase.”Bioorg Med Chem.6(6):6876-94 (1998).
Keller et al. “Mechanism of aminobisphosphonate action: characterization of alendronate inhibition of the isoprenoid pathway.”Biochem Biophys Res Commun.266:560-563 (1999).
Luckman et al. “Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras.”J. Bone Miner. Res.13(4):581-589 (1998).
Martin et al. “Bisphosphonates inhibit the growth ofTrypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, andPlasmodium faiciparum: a potential route to chemotherapy.”J. Med. Chem.44(6):909-916 (2001).
McKenna et al. “The facile dealkylation of phosphonic acid dialkyl esters by bromotrimethylsilane.”Tetrahedron Lett.18:155-158 (1977).
Moomaw et al. “Mammalian protein geranylgeranyltransferase. Subunit composition and metal requirements.”J. Biol. Chem.267:17438-17443 (1992).
Reiss et al. “Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides.”Cell62(1):81-8 (1990).
Reszka et al. “Bisphosphonates Act Directly on the Osteoclast to Induce Caspase Cleavage of Mst1 Kinase during Apoptosis.”J. Biol. Chem.274:34967-34973 (1999).
Sagami et al. “Studies on geranylgeranyl diphosphate synthase from rat liver: specific inhibition by 3-azageranylgeranyl diphosphate.”Arch Biochem Biophys.297(2):314-320 (1992).
Shull et al., “Synthesis and biological activity of isoprenoid bisphosphonates”,Bioorg Med Chem., 14(12), 4130-4136 (2006).
Spear et al. “Molecular cloning and promoter analysis of the rat liver farnesyl diphosphate synthase gene.”J. Biol. Chem.267: 14462-14469 (1992).
Szabo et al. “Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents.”J Med Chem.45(11):2185-2196 (2002).
van Beek et al. “Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates.”Biochem Biophys Res Commun.264(1):108-111 (1999).
van Beek et al. “The role of geranylgeranylation in bone resorption and its suppression by bisphosphonates in fetal bone explants in vitro: A clue to the mechanism of action of nitrogen-containing bisphosphonates.”J Bone Miner Res.14(5):722-729 (1999).
Vepsäläinen et al. “Bisphosphonate prodrugs: a new synthetic strategy to tetraacyloxymethyl esters of methylenebisphosphonates.”Tetrahedron. Lett.40:8491-8493 (1999).
Vicent et al. “The Branch Point Enzyme of the Mevalonate Pathway for Protein Prenylation Is Overexpressed in theob/obMouse and Induced by Adipogenesis.”Mol. Cellular Biol.20:2158-2166 (2000).
Virtanen et al. “Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway,”Cancer Res.62(9):2708-2714 (2002).
Xing et al. “Lovastatin is antiarrhythmic in ischemic heart tissue by blocking triggered activity.”J. of Invest. Med.53(2):S368 (2005).
Yokoyama et al. “Purification of a mammalian protein geranylgeranyltransferase. Formation and catalytic properties of an enzyme-geranylgeranyl pyrophosphate complex.”J Biol Chem.268(6):4055-4060 (1993).
Zenitani et al. “Gerfelin, a novel inhibitor of geranylgeranyl diphosphate synthase fromBeauveria

Affiliated with

Also associated with

Rating

Geranylgeranyl pyrophosphate synthase inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Geranylgeranyl pyrophosphate synthase inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Geranylgeranyl pyrophosphate synthase inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3774719