Methods for producing novel conjugates of thrombin inhibitors

Details Methods for producing novel conjugates of thrombin inhibitors Methods for producing novel conjugates of thrombin inhibitors

1998-07-01

1999-08-24

Mach, D. Margaret M.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D21502

Patent

active

059426209

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: 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: 5112615 (1992-05-01), Ito et al.
patent: 5141947 (1992-08-01), Tamao et al.
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: 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: 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: 5637599 (1997-06-01), Levy et al.
patent: 5679690 (1997-10-01), Andre et al.
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).
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).
Chemical Abstracts 128:29, abstract of Takahashi, 1995.
Chemical Abstracts 125:321384, Jones, 1995.
Chemical Abstracts 124:332313, Matsuzaki, 1995.

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