Nitriles useful as reversible inhibitors of cysteine proteases

Details Nitriles useful as reversible inhibitors of cysteine proteases Nitriles useful as reversible inhibitors of cysteine proteases

2006-01-03

2006-01-03

McKenzie, Thomas C. (Department: 1624)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C514S237200, C514S237500, C514S329000, C514S426000, C514S482000, C544S130000, C544S141000, C544S144000, C544S163000, C546S215000, C548S557000, C558S393000

Reexamination Certificate

active

06982263

ABSTRACT:
Disclosed are novel nitrile compounds of formula (I) further defined herein, which compounds are useful as reversible inhibitors of cysteine proteases such as cathepsin K, S, F, L and B. These compounds are useful for treating diseases and pathological conditions exacerbated by these proteases such as, but not limited to, osteoporosis, rheumatoid arthritis, multiple sclerosis, asthma and other autoimmune diseases, Alzheimer's disease, atherosclerosis. Also disclosed are processes for making such novel compounds.

REFERENCES:
patent: 4021224 (1977-05-01), Pallos et al.
patent: 4137070 (1979-01-01), Pallos et al.
patent: 4267174 (1981-05-01), Berger et al.
patent: 4282212 (1981-08-01), Berger et al.
patent: 4321194 (1982-03-01), Bosies et al.
patent: 4409236 (1983-10-01), Bosies et al.
patent: 4410532 (1983-10-01), Bosies et al.
patent: 5714471 (1998-02-01), Rowe et al.
patent: 5776718 (1998-07-01), Palmer et al.
patent: 6143774 (2000-11-01), Heckmann et al.
patent: 6395897 (2002-05-01), Cywin et al.
patent: 6420364 (2002-07-01), Emmanuel
patent: 6492362 (2002-12-01), Graupe et al.
patent: 2003/0105099 (2003-06-01), Graupe et al.
patent: 2004/0014796 (2004-01-01), Graupe et al.
patent: WO 92/22570 (1992-12-01), None
patent: WO 94/10155 (1994-05-01), None
patent: WO 96/40737 (1996-12-01), None
patent: WO 97/17339 (1997-05-01), None
patent: WO 99/24460 (1999-05-01), None
patent: WO 00/38687 (2000-07-01), None
patent: WO 00/39115 (2000-07-01), None
patent: WO 00/48993 (2000-08-01), None
patent: WO 00/49007 (2000-08-01), None
patent: WO 00/55124 (2000-09-01), None
patent: WO 00/59881 (2000-10-01), None
patent: WO 01/09110 (2001-02-01), None
patent: WO 01/17562 (2001-03-01), None
patent: WO 01/17959 (2001-03-01), None
patent: WO 01/18216 (2001-03-01), None
patent: WO 01/77073 (2001-10-01), None
patent: WO 01/87828 (2001-11-01), None
patent: WO 02/098850 (2002-12-01), None
Wolff, Manfred E. “Burger's Medicinal Chemistry, 5ed, Part I”, John Wiley & Sons, 1995, pp. 975-977.
Banker, G.S. et al, “Modern Pharmaceutics, 3ed.”, Marcel Dekker, New York, 1996, pp. 451-596.
Marquis, Robert W., Ann. Reports Med. Chem., vol. 35, pp. 309-320, 2000.
Riese R.J. et al, J. Clin. Invest., 101(11), pp. 2351-2363, 1998.
Saegusa K,, et al, J Clin Invest. Aug. 2002;110(3):361-9.
Thurmond RL et al, J Pharmacol Exp Ther. Oct. 17, 2003, abstract cited in PMID: 14566006.
Mary J. Bossard, et al. “Proteolytic Activity of Human Osteoclast Cathepsin K” J. Biol. Chem., vol. 271, No. 21, May 24, 1996, pp. 12517-12524.
Harold A. Chapman, et al. “Emerging Roles for Cysteine Proteases in Human Biology”, Ann. Rev. Physiol. 1997, 59:63-88.
Harold A. Chapman, et al. “Endosomal Proteolysis and MHC Class II Function” Curr. Opinion in Immunol. 1998, 10:93-102.
Fred H. Drake, et al, “Cathepsin K, but Not Cathepsins B, L, or S, Is Abundantly Expressed in Human Osteoclasts” J. Biol. Chem. 1996, vol. 271, No. 21, pp. 12511-12516.
Juan C. Engel, et al. “Cysteine Protease Inhibitors Cure an Experimental Trypanosoma cruzi Infection” J. Exp. Med. vol. 188, No. 4, 1998, pp 725-734.
Bruce D. Gelb, et al. “Pycnodysostosis, a Lysosomal Disease Caused by Cathepsin K Deficiency” Science, vol. 273, No. 5279, pp 1236-1238 1996.
Maxine Gowen “Inhibition of cathepsin K—a novel approach to antiresorptive therapy” Exp. Opin. Invest. Drugs (1997) 6(9):1199-1202.
Maxine Gowen “Cathepsin K Knockout Mice Develop Osteopetrosis Due to a Deficit in Matrix Degradation but Not Demineralization” J. Bone and Mineral Research vol. 14, No. 10, 1999 pp 1654-1663.
Wu-Shiun Hou “Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis” J. Clin. Invest. vol. 103, No. 5:731-738 1999.
Klaus M. Hummel, et al. “Cysteine Proteinase Cathepsin k mRNA Is Expressed in Synovium of Patients with Rheumatoid Arthritis and is Detected at Sites of Synovial Bone Destruction” J. Rheumatology 1998: 25:10 pp 1887-1894.
Woomi Kim, et al. “Recent developments of cathepsin inhibtors and their selectivity” Exp. Opin. Ther. Patents (2002) 12(3):419-432.
Cynthia A. Lemere, et al. “The Lysosomal Cysteine Protease, Cathepsin S, Is Increased in Alzheimer's Disease and Down Syndrome Brain” Am. J. Pathology vol. 146, No. 4, 1995, pp 848-860.
Amanda J. Littlewood-Evans, et al. “The Osteoclast-associated Protease Cathepsin K Is Expressed in Human Breast Carcinoma” Cancer Research vol. 57, pp 5386-5390, 1997.
Robert W. Marquis, et al. “Inhibition of Cysteine Protease” Annual Reports in Medicinal Chemistry, vol. 35, pp 309-320.
Mary Teresa Moran, et al. “Pathologic gene expression in Gaucher disease: up-regulation of cysteine proteinases including osteoclastic cathepsin K” Blood, vol. 96, No. 5 pp 1969-1978 2000.
Ulf Muller-Ladner, et al. “Cysteine proteinases in arthritis and inflammation” Perspectives in Drug Discovery and Design, vol. 6, pp 87-98 1996.
Terry Y. Nakagawa, et al. “Impaired Invariant Chain Degradation and Antigen Presentation and Diminished Collagen-Induced Arthritis in Cathepsin S Null Mice” Immunity, vol. 10, 207-217, 1999.
Jan Potempa, et al. “Host and Porphyromonas gingivalls proteinases in periodonitis: A biochemical model of infection and tissue destruction” Perspectives in Drug Discovery and Design, 2 (1994) 445-458.
Richard J. Riese, et al. “Essential Role for Cathepsin S in MHC Class II-Associated Invariant Chain Processing and Peptide Loading” Immunity, vol. 4, pp 357-366, 1996.
Richard J. Riese, et al. “Cathepsin S Activity Regulates Antigen Presentation and Immunity” J. Clin. Invest. vol. 101, No. 11, 1998, pp 2351-2363.
Gideon A. Rodan, et al. “Therapeutic Approaches to Bone Diseases” Science vol. 289, pp 1508-1514, 2000.
Kaoru Saegusa, et al. “Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity” J. Clin. Invest. 2002, vol. 110, No. 3 pp 361-369.
Paul Saftig, et al. “Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice” Proc. Natl. Acad. Sci. USA, 1998, vol. 95, pp 13453-13458.
Andrey Semenov, et al. “Antimalarial Synergy of Cysteine and Aspartic Protease Inhibitors” Antimicrobial Agents and Chemotherapy 1998, vol. 42, No. 9, pp 2254-2258.
Guo-Ping Shi, et al. “Cathepsin S Required for Normal MHC Class II Peptide Loading and Germinal Center Development” Immunity, vol. 10, pp 197-206, 1999.
Guo-Ping Shi, et al. “Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages” J. Exp. Med. vol. 191, No. 7, 2000, pp 1177-1185.
Ward W. Smith, et al. “Cathepsin K as a target for the treatment of osteoporosis” Expert Opinion on Therapeutic Patents 1999, 9(6):683-694.
Galina K. Sukhova, et al. “Expression of the Elastolytic Cathepsins S and K in human Atheroma and Regulation of their Production in Smooth Muscle Cells” J. Clin. Invest. vol. 102, No. 3, 1998, pp 576-583.
Nobuhiro Suzumori, et al. “Increased concentrations of cathepsin D in peritoneal fluid from women with endometriosis” Mol. Human Reprod. vol. 7, No. 5 pp 459-462, 2001.
Dennis S. Yamashita, et al. “Cathepsin K and the Design of Inhibitors of Cathepsin K” Curr. Pharm. Design, 2000, vol. 6, 1-24.
Tao Zheng, et al. “Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase—and cathepsin-dependent emphysema” J. Clin. Invest. 2000, vol. 106, No. 9, pp 1081-1093.
Howard C. Ansel, et al. “Pharmaceutical Dosage Forms and Drug Delivery Systems” Fifth Edition, Lea & Febiger 1990, pp 51-133.
Atkinson, et al; “Desilylative elimination of the quinazolinone ring from 1-(4-oxoquinazolin-3-yl)-2-silylaziridines; preparation of a

Affiliated with

Also associated with

Rating

Nitriles useful as reversible inhibitors of cysteine proteases does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Nitriles useful as reversible inhibitors of cysteine proteases, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nitriles useful as reversible inhibitors of cysteine proteases will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3534848