.alpha.-ketoamide derivatives as inhibitors of thrombosis

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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514 13, 530324, 530325, 530326, 424 169, 424 9341, A61K 3800, C07K 500, C07K 700, C07K 1700

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active

056704798

ABSTRACT:
a-Ketoamide derivatives, their pharmaceutically acceptable salts, compositions, diagnostic compositions and pharmaceutical compositions, which are useful for preventing or treating in a mammal a pathological condition characterized by thrombosis are described.
a-Ketoamide derivatives, their pharmaceutically acceptable salts, compositions and diagnostic compositions, which are useful for in vivo imaging of thrombi in a mammal are also described.
Methods of preventing or treating in a mammal a pathological condition characterized by thrombosis and methods of in vivo imaging of thrombi in a mammal are also disclosed.

REFERENCES:
patent: 4418052 (1983-11-01), Wong
patent: 4652440 (1987-03-01), Paik et al.
patent: 4957939 (1990-09-01), Gries et al.
patent: 4980148 (1990-12-01), Dean et al.
patent: 5011686 (1991-04-01), Pang
patent: 5024829 (1991-06-01), Berger et al.
patent: 5051405 (1991-09-01), Klein et al.
patent: 5053392 (1991-10-01), Klein et al.
patent: 5118790 (1992-06-01), Winant et al.
patent: 5196404 (1993-03-01), Maraganore et al.
patent: 5240913 (1993-08-01), Maraganore et al.
Boudron et al., FEBS Letters, 294(3):163-166 (Dec. 1991).
DiMaio, et al., J. Med. Chem., 35:3331-3341 (1992).
Fischman et al., J. Nucl. Med., 34(12):2253-2263 (Dec. 1993).
Angelastro et al., ".alpha.-Diketone and .alpha.-Keto Ester Derivatives of N-Protected Amino Acids and Peptides as Novel Inhibitors of Cysteine and Serine Proteinases," J. Med. Chem. 33:11-13 (1990).
Bajusz et al., "Highly Active and Selective Anticoagulants: .sub.D -Phe-Pro-Arg-H, a Free Tripeptide Aldehyde Prone to Spontaneous Inactivation, and Its Stable N-Methyl Derivative, .sub.D -MePhe-Pro-Arg-H", J. Med. Chem. 33:1729-1735 (1990).
Bajusz, "Interaction of Trypsin-Like Enzymes with Small Inhibitors", Symposia Biologica Hungarica 25:277-298 (1984).
Bajusz et al., "Inhibition of Thrombin and Trypsin by Tripeptide Aldehydes," Int. J. Peptide Protein Res. 12:217-221 (1978).
Berndt and Phillips, "Platelet Membrane Proteins: Composition and Receptor Function," Platelets in Biology and Pathology -2, pp. 43-75, Elsevier/North Holland Biomedica Press (1981).
Bourdon et al., "Structure-function relationships of hirulog peptide interactions with thrombin," FEBS 294:163-166 (1991).
Brechbiel et al., "Synthesis of 1-p-Isothiocyanatobenzyl) Derivatives of DTPA and EDTA. Antibody Labeling and Tumor Imaging Studies," Inorg. Chem. 25:2772-2781 (1986).
Brown et al., "Conjugation of Methallothionein to a Murine Monoclonal Antibody," Analytical Biochemistry 172:22-28 (1988).
Califf et al., "Research After Coronary Angioplasty: An Overview," J. Am. Coll. Cardiol. 17:2B-13B (1991).
Chen and Buchanan, "Mitogenic Activity of Blood Components. I. Thrombin and Prothrombin (Chick Embyro Fibroblasts/Growth Factors in Plasma and Serum/Wound Healing)," Proc. Natl. Acad. Sci. USA 72:131-135 (1975).
Church et al., "Chimeric Antithrombin Peptide," The Journal of Biological Chemistry 226:11975-11979 (1991).
Connolly et al.,. "An Inhibitor of Collagen-Simulated Platelet Activation from the Salivary Glands of the Haementeria officinalis Leech," J. Biol. Chem. 267:6893-6898 (1992).
DeRoos et al., "Myocardial infarct sizing and assessment of reperfusion by magnetic resonance imaging: a review," Int. J. Card. Imaging 7:133-138 (1991).
Dixon, "The Graphical Determination of K.sub.m and K.sub.i," Biochem J. 129:197-202 (1972).
Edwards et al., "Design, Synthesis, and Kinetic Evaluation of a Unique Class of Elastase Inhibitors, the Peptidyl .alpha.-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. 114:1854-1863 (1992).
Eidt et al., "Thrombin is an Important Mediator of Platelet Aggregation in Stenosed Canine Coronary Arteries with Endothelial Injury," J. Clin. Invest. 84:18-27 (1989).
Fehrentz and Castro, "An Efficient Synthesis of Optically Active .alpha.-(t-Butoxycarbonylamino)-aldehydes from .alpha.-Amino Acids," Synthesis 7:676-678 (1983).
Fusetani and Matsunaga, "Cyclotheonamides, Potent Thrombin Inhibitors, From a Marine Sponge Theonella sp," J. Am. Chem. Soc. 112:7053-7054 (1990).
Gash et al., "Factors Influencing Reocclusion After Coronary Thrombolysis for Acute Myocardial Infarction," Am. J. Cardiol. 57:175-177 (1986).
Haghiara and Schreiber, "Reassignment of Stereochemistry and Total Synthesis of the Thrombin Inhibitor Cyclotheonamide B," J. Am. Chem. Soc. 114:6570-6571 (1992).
Hladovec, "A Sensitive Model of Venous Thrombosis in Rats," Thrombosis Research 43:539-544 (1986).
Houghten, "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 82:5131-5135 (1985).
Jakubowski and Maraganore, "Inhibition of Coagulation and Thrombin-Induced Platelet Activities by a Synthetic Dodecapeptide Modeled on the Carboxy-Terminus of Hirudin," Blood 75:399-406 (1990).
Jang et al., "In Vivo Thrombin Inhibition Enhances and Sustains Arterial Recanalization With Recombinant Tissue-Type Plasminogen Activator," Cir. Res. 67:1552-1561 (1990).
Jang et al., "Prevention of Platelet-Rich Arterial Thrombosis by Selective Thrombin Inhibition," Circulation 81:219-225 (1990).
Kelly et al., "Hirudin Interruption of Heparin-Resistant Arterial Thrombus Formation in Baboons," Blood 77:1006-1012 (1991).
Kelly et al., "Relative Antithrombotic Potencies and Hemostatic Risks of Reversible D-Phe-Pro-Arg (D-FPR) Antithrombin Derivatives," Thromb. Haemostas. 65:736 at abstract 257 (1991).
Kettner et al., "The Selective Inhibition of Thrombin by Peptides of Boroarginine," J. Biol. Chem. 265:18289-18297 (1990).
Kettner and Shaw, "Inactivation of Trypsin-Like Enzymes with Peptides of Arginine Chloromethyl Ketone," Methods Enzymol. 80:826-842 (1987).
Khaw et al., "Myocardial Infarct Imaging of Antibodies to Canine Cardiac Myosin with Indium-111-Diethylenetriamine Pentaacetic Acid," Science 209:295-297 (1980).
Kline et al., "Hirulog Peptides with Scissile bond Replacements Resistant to Thrombin Cleavage," Biochem. Biophys. Res. Commun. 177:1049-1055 (1991).
Krstenansky et al., "Development of MDL 28,050, a Small Stable Antithrombin Agent Based on a Functional Domain of the Leech Protein, Hirudin," Thrombosis and Haemostasis 63:208-214 (1990).
Krstenansky and Mao, "Antithrombin Properties of C-Terminus of Hirudin Using Synthetic Unsulfated N.sup..alpha. -acetyl-hirudin.sub.45-65," FEBS Lett 211:10-16 (1987).
Kurz et al., "Rat Model of Arterial Thrombosis Induced by Ferric Chloride," Thrombosis Research 60:269-280 (1990).
Levin et al., "Specificity of the Thrombin-Induced Release of Tissue Plasminogen Activator From Cultured Human Endothelial Cells," Thromb. Haemostas. 56:115-119 (1986).
Liu et al., "The Region of the Thrombin Receptor Resembling Hirudin Binds to Thrombin and Alters Enzyme Specificity," J. Biol. Chem. 266:16977-16980 (1991).
Lorand and Konishi, "Activation of the Fibrin Stabilizing Factor of Plasma by Thrombin," Arch. Biochem. Biophys. 105:58-67 (1964).
Mann et al., "Surface-Dependent Reactions of Vitamin K-Dependent Enzyme Complexes," Blood 76:1-16 (1990).
Mao et al., "Interaction of Hirudin with Thrombin: Identification of a Minimal Binding Domain of Hirudin That Inhibits Cloning Activity," Biochemistry 27:8170-8173 (1988).
Maraganore et al., "Anticoagulant Activity of Synthetic Hirudin Peptides," J. Biol. Chem. 264:8692-8698 (1989).
Maraganore et al., "Design and Characterization of Hirulogs: A Novel Class of Bivalent Peptide Inhibitorsr of Thrombin," Biochemistry 29:7095-7101 (1990).
Maraganore et al., "Comparison of Anticoagulant and Antithrombotic Activities of Hirulog-1 and Argatroban (MD-805)," Thromb. Haemostas. 65:651 at abstract 17 (1991).
Marki et al., "Total Solid-Phase Synthesis of Porcine Gut Gastrin Releasing Peptide (GRP), a Mammalian Bombesin," J. Am. Chem. Soc. 103:3178-3185 (1981).
Marki and Wallis, "The Anticoagulant of Antithrombiotic Properties of Hirudins," Thrombosis and Haemostasis 64:344-348 (1990).
Markwardt et al

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