Peptidase inhibitors

Details Peptidase inhibitors Peptidase inhibitors

1995-05-04

1998-04-07

Lukton, David

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

526595, A61K 3805

Patent

active

057365202

ABSTRACT:
This invention relates to analogs of peptidase substrates in which the nitrogen atom of the scissile amide group of the substrate peptide has been replaced by H, an aldehyde, a substituted carbonyl or a substituted malonyl moiety. These analogs of the peptidase substrates provide specific enzyme inhibitors for a variety of proteases, the inhibition of which will have useful physiological consequences in a variety of disease states.

REFERENCES:
patent: 3867364 (1975-02-01), Hamao et al.
patent: 4277395 (1981-07-01), Bey et al.
patent: 4401594 (1983-08-01), Hamao et al.
patent: 4820691 (1989-04-01), Patel
patent: 5081284 (1992-01-01), Higuchi et al.
patent: 5444042 (1995-08-01), Bartus et al.
patent: 5510531 (1996-04-01), Higuchi et al.
patent: 5519048 (1996-05-01), Salituro et al.
J.P. Burkhart et al., Tetrahedron Letters, vol. 29, No. 28, 3433-3436 (1988).
S. Mehdi et al., Biochem. and Biophys. Res. Comm., vol. 166, No.2, 595-600 (1990).
Caner et al, Brain Research, 607, pp. 354-356(1993).
Kitagawa et al, Neuroscience vol. 31, No. 2, pp. 401-411, 1989.
Seubert et al, Brain research, 492, (1989) 366-370.
Lee et al, Proc. Natl. Acad. Sci, USA vol. 88, 7233-7237 Aug. 1991 Neurobiology.
M. Angelastro et al., The Journal of Organic Chemistry vol. 54, No. 16, 3913-3916 (1989).
Medhi et al, Biochemical and Biophysical Research Communications vol. 157, No. 3, pp. 1117-1123, (1988).
Bajusz, S. et al., Intl. J. Peptide Protein Res. 12, 1978, pp. 217-221, "Inhibition of Thrombin and Trypsin by Tripeptide Aldehydes".
Mehdi, S. et al, Biochem and Biophys Res Comm, vol.157, No.3, 1117-1123 (1988).
Kozlowski, K. et al., Proc. Natl. Acad. Sci. USA vol. 81, pp. 1135-1139, Feb., 1984, Cell Biology, "Tumor Cell Proteinase Visualization and Quantification Using a Fluorescent Transition-State Analog Probe".
Peptides, Structure & Function (C.M. Deber et al) Proceedings of the American Peptide Symposium, 1985. Hori, H. et al, "Inhibition of Human Leukocyte Elastase, Procine Pancreatic Elastase and Cathepsin G by Peptide Ketones", pp. 819-822.
Peptides, Structure & Function--Proceedings of the American Peptide Symposium, 1985, Galpin, I.J. et al, "A New Approach to the Synthesis of Peptide Aldehyde Inhibitors", pp. 799-802.
Wang K., "Developing selective inhibitors of Calpain", TIPS, Apr., 1990, vol. 11, pp. 139-142.
Bajusz, S. et al., Peptides, Proceedings of the Seventh American Peptide Symposium, Pierce Chemical Company, Rockford, Illinois, 1981, pp. 417-420, "Structure-Activity Relationships Among the Tripeptide Aldehyde Inhibitors of Plasmin and Thrombin".
Bajusz, S. et al., Peptides: Chemistry, Structure and Biology, Proceedings of the Fourth American Peptide Symposium, Ann Arbor Science Publishers Inc., 1975, "Peptide Aldehyde Inhibitors of the Fibrinogen-Thrombin Reaction". pp. 603-608.
Isabel Charles et al, J.C.S, Perkin I, 1980, pp. 1139-1146.
Cs.-Szabo et al, "Specific inhibition of human granulocyte elastise with peptide aldehydes", FEBS, vol. 195, No. 1,2; pp. 265-268, 1986.
Chemical Abstracts, vol. 107, No. 25, 228458u (1987).
Mehdi, S., TIBS 16, pp. 150-153 (Apr., 1991).
Brorson, J., et al, Stroke, vol. 20, No. 7, pp. 1259-1267 (Jul. 1995).
Longa, E.Z., et al, Stroke, vol. 20, No. 1, pp. 84-91 (Jan., 1989).
Ito, A. et al., "Peptide Aldehydes Inhibiting Chymotrypsin", Biochemical and Biophysical Research Communications, vol. 49, No. 2, pp. 343-349 (1972).
Thompson, R.C., "Use of Peptide Aldehydes to Generate Transition-State Analogs of Elastase",.Biochemistry, vol. 12, No. 1, pp. 47-51 (1973).
Derwent No. 86-163399 (EP185390, published Jun. 25, 1986).
Derwent No. 82-335432 (FR2490632-A, published Mar. 26, 1982).
Derwent No. 84-129431 (J58164563-A, published Sep. 29, 1983).
Saito, M. et al., "Purification and Structure of Novel Cysteine Proteinase Inhibitors..", Agric. Biol. Chem.. 51(3), pp. 861-868 (1987).
Umezawa, H. et al., "Proteinases in Mammalian Cells and Tissues", Elsevier/-North-Holland Biomedical Press, Barrett (ed), Ch. 15, pp.637-646 (1977).
Ogura, K. et al., "Purification and Structure of a Novel Cysteine Proteinase Inhibitor, Strepine P-1", Agric. Ciol. Chem., 49(3), pp. 799-805 (1985).
Chemical Abstracts 146554g, vol. 80, (1974).
Chemical Abstracts 105:24605p, vol. 106 (1986).
Chemical Abstracts 104:125573m, vol. 104 (1986).
Chemical Abstracts 101:192438x, vol. 101 (1984).
Chemical Abstracts 100:205401m, vol. 100 (1984).
Chemical Abstracts 100:187896v, vol. 100 (1984).
Derwent Publication 89-182787/25, Suntory LTD.
Derwent Publication 86-172210/21, Kawaken Fine Chemical KK.
Sasaki, T. et al., "Inhibitory Effect of DI-and Trippeptidyl Aldehydes..", J. Enzyme Inhibiton, vol. 3, pp. 195-201, (1990).
Chemical Abstracts, vol. 111:174674y (1989).
Chemical Abstracts, vol. 101:23948h PCT Intl. Appl:WP84 00 365 (1984).
Chemical Abstracts, vol. 80:146554g (1973).
Thompson, R.C. "Peptide Aldehydes: Potent Inhibitors of Serine and Cysteine Proteases", Methods Enzymol., vol. 46, pp. 220-225 (1977).
Bajusz, S. et al., Peptides: Chemistry, Structure and Biology, Proceedings of the Fourth American Peptide Symposium, Ann Arbor Science Publishers Inc., "Peptide Aldehyde Inhibitors of the Fibrinogen-Thrombin Reaction" (1975) pp. 603-608.
Cs.-Szabo et al, "Specific inhibition of human granulocyte elastise with peptide aldehydes", FEBS, vol. 195, No. 1, 2; pp. 265-268.
Zhaozhao Li et al, "Peptide .alpha.-Keto Ester, .alpha.-Keto Amide, and .alpha.-Keto Acid Inhibitors of Calpains and Other Cysteine Proteases", J. Med. Chem., vol. 36, pp. 3472-3470 (1993).
Chemical Abstracts 100:114752k, vol. 100, (1984).
Chemical Abstracts 100:19717u, vol. 100 (1984).
Chemical Abstracts 97:19651n, vol. 97 (1982).
Chemical Abstracts 90:99132n, vol. 90 (1979).
Chemical Abstracts 87:196211h, vol. 87 (1977).
Chemical Abstracts 86:5859x, vol. 86 (1977).
Chemical Abstracts 85:105947x, vol. 85 (1976).
Smith, R.A. et al., "Inhibition of Cathepsin B by Peptidyl Aldehydes and Ketones..", Biochemistry 27, pp. 6568-6573 (1988).
Grobelny, D. et al., "Inhibition of Angiotensin Converting Enzyme by Aldehyde and Ketone Substrate Analogues", Biochemistry, vol. 25, No. 5, pp. 1072-1078 (1986).
Thompson, R.C. et al., "Reaction of Peptide Aldehydes with Serine Proteases", Bochemistry, vol. 18, No. 8, pp. 1552-1558 (1979).
Chemical Abstracts 99:170031x, vol. 99 (1983).
Medhi et al, "Inhibition of the Proteolysis of Rat Erythrocyte Membrane Proteins by a Synthetic Inhibitor of Calpain"; Biochemical and Biophysical Research Communications vol. 157, No. 3, pp. 1117-1123, (1988).
Hong et al, "Neuroprotection with a Calpain Inhibitor in a Model of Focal Cerebral Ischemia", Stroke, vol. 25, No. 3, pp. 663-669, (Mar. 1994).
Arlinghaus et al, "Improved posthypoxic recovery with a membrane permable calpain inhibitor", European Journal of Pharmacology, vol. 209, pp. 123-125 (1991).
Tsujinaka, T. et al., "Synthesis of a new cell penetrating calpain hihibitor (calpain)", Biochemical and Biophysical Research Communications vol. 153, No. 3, pp. 1201-1208, (1988).
Baron, B.M., et al, Emergency Management and Critical Care of Stroke (meeting disclosure), Germany, Sep. 1996.

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