Methods of treating or preventing thromboses

Details Methods of treating or preventing thromboses Methods of treating or preventing thromboses

1999-06-11

2000-07-11

Seaman, D. Margaret

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

546166, C07D21504, C07D21506, A61K 314709

Patent

active

060873752

ABSTRACT:
Novel compounds comprising chemically reactive intermediates which can react with available reactive functionalities on blood components to form covalent linkages, where the resulting covalently-bound conjugates are found to have thrombin inhibition activity are provided. Specifically, the thrombin inhibitor compounds of the present invention are derivatives of the known thrombin inhibitor argatroban, which can be covalently linked to chemically reactive functionalities on various blood components. The conjugated thrombin inhibitors thereby have extended lifetimes in the bloodstream, as compared to the unconjugated parent drug, and are, therefore, capable of maintaining thrombin inhibitory activity for extended periods of time as compared to the unconjugated parent drug. Also provided herein are methods for inhibiting thrombin activity in vivo comprising administering to the bloodstream of a mammalian host the novel compounds of the present invention.

REFERENCES:
patent: 3622615 (1971-11-01), Nicolaides et al.
patent: 3978045 (1976-08-01), Okamoto et al.
patent: 3992530 (1976-11-01), Foell et al.
patent: 4018913 (1977-04-01), Okamoto et al.
patent: 4018915 (1977-04-01), Okamoto et al.
patent: 4036955 (1977-07-01), Okamoto et al.
patent: 4041156 (1977-08-01), Okamoto et al.
patent: 4046876 (1977-09-01), Okamoto et al.
patent: 4049645 (1977-09-01), Okamoto et al.
patent: 4055636 (1977-10-01), Okamoto et al.
patent: 4055651 (1977-10-01), Okamoto et al.
patent: 4062963 (1977-12-01), Okamoto et al.
patent: 4066758 (1978-01-01), Okamoto et al.
patent: 4066759 (1978-01-01), Okamoto et al.
patent: 4066773 (1978-01-01), Okamoto et al.
patent: 4069317 (1978-01-01), Okamoto et al.
patent: 4069318 (1978-01-01), Okamoto et al.
patent: 4069323 (1978-01-01), Okamoto et al.
patent: 4069329 (1978-01-01), Okamoto et al.
patent: 4070457 (1978-01-01), Okamoto et al.
patent: 4071621 (1978-01-01), Okamoto et al.
patent: 4072743 (1978-02-01), Okamoto et al.
patent: 4072744 (1978-02-01), Okamoto et al.
patent: 4072757 (1978-02-01), Okamoto et al.
patent: 4073891 (1978-02-01), Okamoto et al.
patent: 4073892 (1978-02-01), Okamoto et al.
patent: 4073913 (1978-02-01), Okamoto et al.
patent: 4073914 (1978-02-01), Kikumoto et al.
patent: 4073916 (1978-02-01), Okamoto et al.
patent: 4093712 (1978-06-01), Okamoto et al.
patent: 4096255 (1978-06-01), Kikumoto et al.
patent: 4097472 (1978-06-01), Okamoto et al.
patent: 4097591 (1978-06-01), Okamoto et al.
patent: 4101653 (1978-07-01), Okamoto et al.
patent: 4104392 (1978-08-01), Okamoto et al.
patent: 4108986 (1978-08-01), Okamoto et al.
patent: 4117127 (1978-09-01), Okamoto et al.
patent: 4125604 (1978-11-01), Okamoto et al.
patent: 4125619 (1978-11-01), Okamoto et al.
patent: 4131673 (1978-12-01), Okamoto et al.
patent: 4133880 (1979-01-01), Okamoto et al.
patent: 4139529 (1979-02-01), Okamoto et al.
patent: 4140681 (1979-02-01), Okamoto et al.
patent: 4154828 (1979-05-01), Okamoto et al.
patent: 4168307 (1979-09-01), Okamoto et al.
patent: 4173630 (1979-11-01), Okamoto et al.
patent: 4201863 (1980-05-01), Okamoto et al.
patent: 4258192 (1981-03-01), Okamoto et al.
patent: 4537896 (1985-08-01), Claeson et al.
patent: 4816560 (1989-03-01), Verdini et al.
patent: 4822788 (1989-04-01), Kishimoto et al.
patent: 4977168 (1990-12-01), Bernat et al.
patent: 5122615 (1992-06-01), Ito et al.
patent: 5141947 (1992-08-01), Tamao
patent: 5196404 (1993-03-01), Maraganore et al.
patent: 5240913 (1993-08-01), Maraganore et al.
patent: 5242810 (1993-09-01), Maraganore et al.
patent: 5274098 (1993-12-01), Stiier et al.
patent: 5332822 (1994-07-01), Misra
patent: 5371091 (1994-12-01), Misra et al.
patent: 5424291 (1995-06-01), Atrash et al.
patent: 5457114 (1995-10-01), Stuber et al.
patent: 5458568 (1995-10-01), Racchini et al.
patent: 5484772 (1996-01-01), Sall et al.
patent: 5488037 (1996-01-01), Sall et al.
patent: 5492895 (1996-02-01), Vlasuk et al.
patent: 5506241 (1996-04-01), Mano et al.
patent: 5510330 (1996-04-01), Martin et al.
patent: 5514409 (1996-05-01), Maraganore et al.
patent: 5552410 (1996-09-01), Galtier et al.
patent: 5558642 (1996-09-01), Schweich et al.
patent: 5559150 (1996-09-01), Soll
patent: 5561146 (1996-10-01), Kim
patent: 5565471 (1996-10-01), Ozaki
patent: 5571844 (1996-11-01), Stuber et al.
patent: 5578594 (1996-11-01), Ackermann et al.
patent: 5583113 (1996-12-01), Berry et al.
patent: 5583146 (1996-12-01), Kimball et al.
patent: 5588962 (1996-12-01), Nicholas et al.
patent: 5597804 (1997-01-01), Webb et al.
patent: 5605892 (1997-02-01), Ikejiri et al.
patent: 5607952 (1997-03-01), Badorc et al.
patent: 5612369 (1997-03-01), Bone et al.
patent: 5612378 (1997-03-01), Tianbao et al.
patent: 5626562 (1997-05-01), Castro
patent: 5635477 (1997-06-01), Degrado et al.
patent: 5637599 (1997-06-01), Levy et al.
patent: 5679690 (1997-10-01), Andre et al.
patent: 5713853 (1998-02-01), Clark et al.
Bagdanov, et al., Long-Circulating Blood Pool Imaging Agents, Advanced Drug Delivery Reviews 16:335-48 (1995).
Brummel, et al., A Mass Spectrometric Solution to the Address Problem of Combinatorial Libraries, Science 264:399-401 (1994).
Gordon, et al., Applications of Combinatorial Technologies to Drug Discovery. 2. Combinatorial Organic Synthesis, Library Screening Strategies, and Future Directions, J. Med. Chem. 37(10):1385-1401 (1994).
Kerr, et al., Encoded Combinatorial Peptide Libraries Containing Non-Natural Amino Acids, J. Am. Chem. Soc. 115(6):2529-31 (1993).
Kluger, et al., Trimesoyltris(3,5-Dibromosalicylate): Specificity of Reactions of a Trifunctional Acylating Agent with Hemolobin, J. Am. Chem. Soc. 114:9275-79 (1992).
Krantz, Red Cell-Mediated Therapy: Opportunities and Challenges, Blood Cells, Molecules, and Diseases 23(3):58-68 (1997).
Kumada, et al., Comparative Study on Heparin and a Synthetic Thrombin Inhibitor No. 805 (MD-805*) in Experimental Antithrombin III-Deficient Animals, Thrombosis Research 24(4):285-98 (1981).
Kumon, et al., Anticoagulation with a Synthetic Thrombin Inhibitor After Cardiovascular Surgery and for Treatment of Disseminated Intravascular Coagulation, Critical Care Medicine 12(12):1039-43, 1104 (1984).
Magnani, et al., Preparation and Characterization of Biotinylated Red Blood Cells, Biotechnol. Appl. Biochem. 20:335-45 (1994).
Okamoto, et al., Potent Inhibition of Thrombin by the Newly Synthesized Arginine Derivative No. 805. The Importance of Stereostructure of its Hydrophobic Carboxamide Portion, Biochem. and Biophys. Res. Comm. 101(2):440-46 (1981).
Ota, et al., Clinical Evaluation of a New Thrombin Inhibitor Available for Haemodialysis, Proc. EDTA 20:144-49 (1983).
Rawson, et al., Separation of 21-(R)- and 21-(S)-Argatroban: Solubility and Activity of the Individual Diastereoisomers, J. Pharm. Sci. 82(6):672-73 (1983).
Sorensen, et al., Identification of the Interleukin-3 Receptor Using an Iodinatable, Cleavable, Photoreative Cross-Linking Agent, J. Biol. Chem. 261(20):9094-97 (1986).
Suzuki, et al., Biotinylated Erythrocytes: In Vivo Survival and In Vitro Recovery, Blood 70(3):791-95 (1987).
Taylor, et al., in Vivo Binding and Clearance of Circulating Antigen by Bispecific Heteropolymer-Mediated Binding to Primate Erythrocyte Complement Receptor, J. Immunol. 148(8): 2462-68 (1992).
Taylor, et al., Use of Heteropolymeric Monoclonal Antibodies to Attach Antigens to the C3b Receptor of Human Erythrocytes: a Potential Therapeutic Treatment, Proc. Natl. Acad. Sci. USA, 88:3305-09 (1991).
Titus, et al., Humna K/Natural Killer Cells Targeted with Hetero-Cross-Linked Antibodies Specifically Lyse Tumor Cells In Vitro and Prevent Tumor Growth In Vivo, J. Immunol. 139(9):3153-58 (1987).
Wakai, et al., Studies on Antigenicity of Argipidine (MD-805), Jpn. Pharmacol. Ther. 14:197-206, Supp. 5 (1986).
Wilson, et al., Rapid Whole Blood Assay for HIV-1 Seropositivity Using an Fab-Peptide Conjugate, J. Immunol. Methods 138(1):111-19 (1991) (Abstract).
Yokoyama, et al., Deferoxamine, a Promising Bifunctional Chelating Agent for Labeling Proteins with Gallium: Ga-67 DF-HSA: Concise Communication, J. Nucl. Med. 23:909-14 (1982).
Chemi

Affiliated with

Also associated with

Rating

Methods of treating or preventing thromboses does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods of treating or preventing thromboses, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of treating or preventing thromboses will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-542752