Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1993-09-14
1995-07-04
Warden, Jill
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530331, A61K 3800, C07K 508
Patent
active
054300231
ABSTRACT:
Thrombin inhibitors represented by the formula ##STR1## as provided wherein A(C.dbd.O)-- is, inter alia, phenylglycyl, cyclohexylglycyl, cyclohexenylglycyl, thienylglycyl or naphthylglycyl, wherein the .alpha.-amino group is preferably substituted by alkyl e.g. methyl or an alkoxycarbonyl, cycloalkoxycarbonyl or arylkoxycarbonyl group e.g. t-butyloxycarbonyl. A(C.dbd.O)-- also represents an .alpha.-substituted acetyl group such as .alpha.-methoxyphenylacetyl; or a bicyclic group such as a tetrahydroisoquinolin-1- or 3-carbonyl group; a perhydroisoquinolin -1- or -3-carbonyl group; or a 1-amino or (substituted amino) cycloalkylcarbonyl group such as 1-aminocyclohexylcarbonyl. Also provided are a method for inhibiting the formation of blood clots in man and animals by administering a thrombin inhibitor of the above formula and pharmaceutical formulations useful in the method.
REFERENCES:
patent: 4316889 (1982-02-01), Bajusz et al.
patent: 4346078 (1982-08-01), Bajusz et al.
patent: 4399065 (1983-08-01), Bajusz et al.
patent: 4478745 (1984-10-01), Bajusz et al.
patent: 4703036 (1987-10-01), Bajusz et al.
patent: 5202416 (1993-04-01), Stueber et al.
Clinical Laboratory Methods and Diagnosis, ed. A. C. Sonnenwirth and L. Jarett, v.1, Chapters 42 and 45, pp. 1020-1025 and 1056 (1980).
Merck Manual of Diagnosis and Therapy, 15th Ed (1987), Merck, Sharp & Dohme Laboratories, Ch 99, pp. 1145-1154.
Zoology, Elliot, A. M., The Meredith Corporation (1968) pp. 725-734.
Goodman and Gilman, The Pharmacological Basis of Therapeutics, Eighth Edition, pp. 1311-1313 (1990).
Sigma Co. Catalog, p. 154 (1992).
Exert, Peptide and Protein Drug Delivery, Vincint Lee, ed. Marcel Dekker, Inc., pp. 288-290 (1991).
Dayhoff, Atlas of Protein Sequence and Structure, 1972, pp. 85-99.
Bagusz, S., et al., J. Med. Chem., 1990, 33, 1729-1735.
Fareed, J., et al., Annals N.Y. Academy of Sciences, 1981, 765-784.
Shuman, et al., Proceedings of the Twelfth American Peptide Symposium, Jun. 16-21, 1991.
Wilson, et al., American Heart Association, Nov. 11-14, 1991, Anaheim Convention Center, Anaheim, Calif.
Bajusz, et al., Int. J. Peptide Res., 12, 1978, 217-221.
Gesellchen, et al., Tenth American Peptide Symposium, May 23-28, 1987, St. Louis, Mo.
Claeson, et al., Proceedings of the Twelfth American Peptide Symposium, Jun. 16-21, 1991, Cambridge, Mass.
Smith, G. F., Shuman, R. T. Gesellchen, P. D., Craft, T. J., Gifford, P., Kurz, K. D., Jackson, C. V. Sandusky, G. E., and P. D. Williams. A New Family of Thrombin Inhibitors with Improvided Specificity and Therapeutic Index. (Submitted to the American Heart Association, Oct., 1991, Circulation Oct., 1991, vol. 84, II-579, 1991).
Jackson, V., Wilson, H., Frank, J., Crowe, V., Craft, T., and G. Smith. The Thrombin Inhibitor, Methyl-D-Phe-Pro-Arginal--An Effective Adjunct to Coronary Artery Thrombolysis in the Anesthetized Dog. FASEB J. 5(4)A521 (1991).
Crowe, V., Frank, J., Wilson, H., Coffman, B., Smith, G., and V. Jackson. Anticoagulant and Antithrombotic Efficacy of the Thrombin Inhibitor Methyl-D-Phe-Pro-Arginal in a Canine Model of Coronary Thrombosis. FASEB J. 5(4)A521 (1991).
Wilson, H., Frank, J., Crowe, V., Coffman, B., Smith, G., Shuman, R., and V. Jackson. Anticoagulant and Antithrombotic Efficacy of the Novel Thrombin Inhibitor, Methyl-D-Phe-Pro-Arginal, in a Canine Model of Coronary Thrombosis (Arteriosclerosis and Thrombosis, Oct., 1991).
Jackson, V., Wilson, H., Frank, J., Crowe, V., Coffman, B., Shuman, R., and G. Smith. The Novel Thrombin Inhibitor Methyl-D-Phg-Pro-Arginal: An Effective Conjunctive Agent to Coronary Artery Thropmobolysis in the Anesthetized Dog. (Arteriosclerosis and Thrombosis, Oct., 1991).
Shuman, R. T., Rothenberger, R. B., Campbell, C. S. Smith, G. F., Jackson, C. V., Kurz, K. D., and P. D. Gesellchen. Prevention of Reocclusion by a Thrombin Inhibitor. (American Peptide Symposium, Jun., 1991).
Shuman, R. T., Rothenberger, R. B., Campbell, C. S., Smith, G. F., Jackson, C. V., Kurz, K. D., and P. D. Gesellchen. A Series of Highly Active Serine Proteinase Inhibitors. (American Peptide Symposium, Jun., 1991).
Jackson, C. V., Frank, J. D., Crowe, V. G., Craft, T. J., and G. F. Smith. Assessment of the Anticoagulant and Antithrombotic Efficacy of the Thrombin Inhibitor, BOC-Phe-Pro-Arginal, in a Canine Model of Coronary Thrombosis. Arteriosclerosis, 10 922A (1990).
Jackson, C. V., Frank, J. D., Crowe, V. G., Craft, T. J., and G. F. Smith. The Thrombin Inhibitor, BOC-Phe-Pro-Arginal. An Effective Adjunct to Coronary Artery Thrombolysis in the Anesthetized Dog. Arteriosclerosis, 10 923a (1990).
Shackelford, K. A., Tanzer, R. L., Shuman, R., Gesellchen, P:.D., Grindey, G. B., Sundboom, J. L. Smith, G. F., and R. L. Merriman. Inhibition of Spantaneous Metastasis by Boc-D-Phe-Pro-Arginal. American Association for Cancer Research, San Francisco, 1989. Proc. Am. Assn. Cancer Res., 30 86, 1989.
Neubauer, B. L., Clemens, J. A., Gesellchen, P. D., Hirsch, K. S., Hoover, D. M., Merriman, R. L., and G. F. Smith. Endocrine Characterization and Sensitivity of the PAIII Prostatic Adenocarcinoma in Male Lobund Wistar (LW) Rats to Anti-fibrin Agents. American Association for Cancer Research. New Orleans, May 1988, Proc. Am. Assn. Cancer Res., 29 240 (1988).
Neubauer, B. L., Best, K. L., Gesellchen, P. D., Goode, R. L., Merriman, R. L., Tanzer, L. R., Shaar, C. J., Shuman, R., Sundboom, J. L. and G. F. Smith. Inhibitory Effects of Heparin and BOC-D-Phe-Pro-Arginal on the Metastasis of the PAIII Prostatic Adenocarcinoma in Male Lobund Wistar (LW) Rats. American Urological Association. Boston, May 1988, J. Urol., 139 175A (1988).
Gesellchen, P. D., Smith, G. F., et al., Anticoagulant, Antithrombotic, and Antimetastatic Effects of a Serine Proteinase Inhibitor. 10th American Peptide Symposium, Washington University, St. Louis, Mo. (1987).
Smith, G. F., Sundboom, J. L., Best, K., Gesellchen, P. D., Merriman, R. L., Shuman, R., and Neubauer, B. L. Heparin, Boc-D-Phe-Pro-Arginal, and Warfarin (Fibrin Antagonists) Inhibit Metastasis in an In Vivo Model. American Chemical Society National Meeting. Abstract BIOL 70 Biochemistry (1987).
K. D. Kurz, T. Smith, R. A. Moore, and B. W. Main. Comparison of Thrombin Inhibitors in Rat Models of Thrombosis and Thrombolysis. FASEB Journal, vol. 5 (No. 4), 1991.
Tomori et al., Chromatographia, vol. 19, 437-442 (1984).
European Search Report for EP 91308785.4.
J. of Medicinal Chemistry--1993.
Eur. Pat. 48982--not provided.
Gesellchen Paul D.
Shuman Robert T.
Boone David E.
Dahling Gerald V.
Demeter John C.
Eli Lilly and Company
Touzeau P. Lynn
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