Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing
Reexamination Certificate
2006-04-18
2006-04-18
Jones, Dameron L. (Department: 1618)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
C424S001110, C424S001650, C514S349000, C546S297000
Reexamination Certificate
active
07029654
ABSTRACT:
Aminoguanidine and alkoxyguanidine compounds are described, including compounds of the Formula VII:wherein X is O or NR9and Het, R1, R7, R8, R12—R15, Ra, Rb, Rc, Z, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing such compounds. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents. Additionally, the compounds can be detectably labeled and employed for in vivo imaging of thrombi.
REFERENCES:
patent: 4097472 (1978-06-01), Okamoto et al.
patent: 4418052 (1983-11-01), Wong
patent: 4980148 (1990-12-01), Dean
patent: 5011686 (1991-04-01), Pang
patent: 5024829 (1991-06-01), Berger et al.
patent: 5466811 (1995-11-01), Alexander
patent: 5656600 (1997-08-01), ABelman et al.
patent: 5656645 (1997-08-01), Tamura et al.
patent: 5658885 (1997-08-01), Lee et al.
patent: 5658930 (1997-08-01), Tamura et al.
patent: 5891909 (1999-04-01), Soll et al.
patent: 6037356 (2000-03-01), Lu et al.
patent: 6204263 (2001-03-01), Lu et al.
patent: 6235778 (2001-05-01), Tomczuk et al.
patent: 6245763 (2001-06-01), Lu et al.
patent: 6326492 (2001-12-01), Wang et al.
patent: 6350764 (2002-02-01), Lu et al.
patent: 6472399 (2002-10-01), Lu et al.
patent: 6566379 (2003-05-01), Lu et al.
patent: 6706021 (2004-03-01), Lu et al.
patent: 0 363 284 (1990-04-01), None
patent: 174261 (1966-02-01), None
patent: 328634 (1978-12-01), None
patent: 938739 (1982-10-01), None
patent: WO 95/07291 (1995-03-01), None
patent: WO 96/18644 (1996-06-01), None
patent: WO 97/01338 (1997-01-01), None
patent: WO 97/30708 (1997-08-01), None
patent: WO 98/23565 (1998-06-01), None
patent: WO 01/04117 (2001-01-01), None
Barrett, A.J., “Proteinase Inhibitors: Potential Drugs!”,Enzyme Inhibitors as Drugs, 1980, Sandler, M., ed., The Macmillan Press Ltd., London, England, 219-229.
Brown, F.J. et al., “Design of Orally Active, Non Peptidic Inhibitors of Human Leukocyte Elastase”,J. Med. Chem., 1994, American Chemical Society, 37, 1259-1261.
Claeson, G., “Synthetic Peptides and Peptidomimetics as Substracts and Inhibitors of Thrombin and Other Proteases in the Blood Coagulation System”,Blood Coagulation and Fibrinolysis, 1994, 5, 411-436, Rapid Communications.
Coughlin, S.R., “Molecular Mechanisms of Thrombin Signaling”,Seminars in Hematology, 1994, 31, 270-277, W.B. Saunders Company.
Cuypers, H.T. et al., “Sufhydryl Content of Bovine Eye Lens Leucine Aminopeptidase. Determination of the Reactivity of the Sulfhydryl Groups of the Zinc Metalloenzyme, of the Enzyme Activated by Mg2, Mn2+, and Co2+, and of the Metal-Free Apoenzyme”,J. Biol. Chem., 1982, 257, 7086-7091, American Society of Biological Chemists, Inc.
De Roos, A. et al., “Myocardial Infarct Sizing and Assessment of Reperfusion by Magnetic Resonance Imaging: A Review”,Int. J. Cardiac Imaging, 1991, 7, 133-138.
Edwards, P.D. et al., “Design, Synthesis, and Kinetic Evaluation of a Unique Class of Elastase Inhibitors, the Peptidyl, α-Ketobenzoxazoles, and the X-ray Crystal Structure of the Covalent Complex between Porcine Pancreatic Elastase and Ac-Ala-Pro-Val-2-Benzoxazole”,J. Am. Chem. Soc., 1992, 114, 1854-1863, American Chemical Society.
Harker, L.A., “Strategies for Inhibiting the Effects of Thrombin”,Blood Coagulation and Fibrinolysis, 1994, 5, S47-S58.
Jeong, J.H. et al., “Cyclic Guanidino-Sugars with Low pKa as Transition-State Analog Inhibitors of Glycosidases: Neutral Instead of Charged Species are the Active Forms”,J. Am. Chem. Soc., 1996, 118, 4227-4234, American Chemical Society.
Kim, K.S. et al., “Preparation of Argatroban Analog Thrombin Inhibitors with Reduced Basic Guanidine Moiety, and Studies of their Cell Permeability and Antithrombotic Activities”,Med. Chem Res., 1996, 6, 377-383.
Lefkovits, J. et al., “Direct hrombin Inhibitors in Cardiovascular Medicine”,Circulation, 1994, 90, 1522-1536, American Heart Association, Inc..
Mack, H. et al., “Design, Synthesis and Biological Activity of Novel Rigid Amidino-Phenylalanine Derivatives as Inhibitors of Thrombin”,J. Enzyme Inhibition, 1995, 9, 73-86, Harwood Academic Publishers GmbH.
Powers, W.J. et al., “Indium-111 Plateley Scintigraphy in Cerebrovascular Disease”,Neurology, 1982, 32, 938-943, American Academy of Neurology.
Saulnier, M.G., et al., “An Efficient Method for the Synthesis of Guanidino Prodrugs”,Bioorg. Med. Chem. Lett., 1994, 4, 1985-1990.
Thakur, M.L. et al., “Indium-111 Labeled Platelets: Studies on Preparation and Evaluation of In Vitro and In Vivo Functions”,Thrombosis Res., 1976, 9, 345-357, Pergamon Press, Inc..
Caplus 127:234621, abstract of Lee, S.-I. et al., “Amidino and Guanidino Substituted Boronic Acid Inhibitors of Trypsin-Like Enzymes”, 1997, Accession No:. 594514.
Eurasian Search Report for Application No. 200000578/28, for application filed Jun. 26, 2000.
WPINDEX, Accession No. 1993-218199, Derwent WPI English language abstract for SU 174261.
WPINDEX, Accession No. 1978-L1249A, Derwent WPI English language abstract for SU328634.
Caplus abstract Semple Edward et al,Journal of Medicinal Chemistry, 1996.
Lu Tianbao
Markotan Thomas P.
Siedem Colleen
Tomczuk Bruce E.
Jones Dameron L.
Ortho-McNeil Pharmaceuticals, Inc.
Woodcock & Washburn LLP
LandOfFree
Heteroaryl aminoguanidines and alkoxyguanidines and their... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Heteroaryl aminoguanidines and alkoxyguanidines and their..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Heteroaryl aminoguanidines and alkoxyguanidines and their... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3560703