Serine protease inhibitors

Details Serine protease inhibitors Serine protease inhibitors

1998-06-03

1999-12-14

Russel, Jeffrey E.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 19, 530331, 544319, A61K 3805, A61K 3806, C07K 506, C07K 5078

Patent

active

060018143

ABSTRACT:
The present invention relates to certain substituted oxadiazole nonpeptides, which are useful as inhibitors of human neutrophil elastase (HNE) for the treatment of HNE-mediated processes implicated in conditions such as adult respiratory distress syndrome, septic shock and multiple organ failure. A series of studies also have indicated the involvement HNE in myocardial ischemia-reperfusion injury, emphysema. HNE-mediated processes are implicated in other conditions such as arthritis, periodontal disease, glomerulonephritis, dermatitis, psoriasis, cystic fibrosis, chronic bronchitis, atherosclerosis, Alzheimer's disease, organ transplantation, corneal ulcers, and invasion behavior of malignant tumors.

REFERENCES:
patent: 4338453 (1982-07-01), Gall
patent: 5055450 (1991-10-01), Edwards et al.
patent: 5164371 (1992-11-01), Edwards et al.
patent: 5550139 (1996-08-01), Groutas
patent: 5618792 (1997-04-01), Gyorkos et al.
Edwards, P. D., et al. "Peptidyl Alpha-Ketoheterocyclic Inhibitors of Human Neutrophil Elastase, 3. In Vitro and in Vivo Potency of a Series of Peptidyl Alpha-Ketobenzoxazoles," J. Med. Chem. 38, 3972-3982 (1995).
Edwards, P. D., et al. "Nonpeptic Inhibitors of Human Neutrophil Elastase. 7. Design, Synthesis, and in Vitro Activity of a Series of Pyridopyrimidine Trifluoromethyl Ketones," J. Med. Chem. 39, 1112-1124 (1996).
Edwards, P. D., et al. "Peptidyl Alpha-Ketoheterocyclic Inhibitors of Human Neutrophil Elastase. 2. Effect of Varying the Heterocyclic Ring on in Vitro Potency," J. Med Chem. 38, 76-85 (1995).
Veale, C. A., et al. "Non-peptidic Inhibitors of Human Leukocyte Elastase. 4. Design, Synthesis, and in Vitro and in Vivo Activity of a Series of Beta-Carbolinone-Containing Trifluoromethyl Ketones," J. Med. Chem. 38, 86-97 (1995).
Veale, C. A., et al. "Nonpeptidic Inhibitors of Human Leukocyte Elastase. 5. Design, Synthesis, and X-ray Crystallography ofa Series of Orally Active 5-Aminopyrimidin-6-one-Containing Trifluoromethyl Ketones," J. Med. Chem. 38, 98-108 (1995).
Goddard, C. J., "Antiinflammatory 1-Phenylpyrazole-4-Heteroarylalkanoic Acids," J. Heterocyclic Chem., 28, 1607-1612 (1991).
LaMattina, J. L., et al. "Utility of p-Nitrophenyl 3-Bromo-2,2-diethoxypropionate (NPBDP) in Heterocyclic Synthesis," J. Org. Chem. 49, 4800-4805 (1984).
Unangst, P. C., et al. "Novel 1,2,4-Oxadiazoles and 1,2,4-Thiadiazoles as Dual 5-Lipoxygenase and Cyclooxygenase Inhibitors," J. Med. Chem. 35, 3691-3698 (1992).
Kitatani, K., et al. "A Novel Oxazole Synthesis Utilizing Tungsten(VI) Catalyzed Decomposition of Alpha-Diazo Carbonyl Compounds in Nitriles," Tet. Lett. 16, 1531-1532 (1974).
Wiley, R. H., "Chemistry of the Oxazoles," Chem. Rev. 37, 401-442 (1945).
Davidson, D., et al. "The Action of Ammonia on Benzoin," J. Org. Chem. 2, 328-334 (1937).
Wiegand, Edwin E., et al. "Polyphosphoric Acid Cyclization of Acetamidoketones to 2,5-Dimethyl-1,3-oxazoles," Synthesis 12, 648-649 (1970).
Wasserman, H.H., et al. "The Oxazole-Triamide Rearrangement. Application To Peptide Synthesis," Tet. Lett. 23, 3831-3834 (1982).
Conforth, J. W., et al. "A New Synthesis of Oxazoles and Iminazoles including its Application to the Preparation of Oxazole." J. Chem Soc. 96-102 (1947).
Conforth, J.W., et al. "Synthesis of Oxazoles from Ethyl Acetoacetate. Ring-fission of Some Oxazole-5-carboxylic Acids." J. Chem. Soc. 93-98 (1953).
Bernstein, P. R., et al. "Nonpeptidic Inhibitors of Human Leukocyte Elastase. 3. Design, Synthesis, X-Ray Crystallographic Analysis, and Structure-Activity Relationships for a Series of Orally Active 3-Amino-6-phenylpyridin-2-one Trifluoromethyl Ketones," J. Med. Chem. 37, 3313-3326 (1994).
Brown, F. J., et al. "Design of Orally Active, Non-Peptidic Inhibitors of Human Leukocyte Elastase," J. Med. Chem. 37, 1259-1261 (1994).
Warner, P., et al. "Non-peptidic Inhibitors of Human Leukocyte Elastase. 1. The Design and Synthesis of Pyridone-Containing Inhibitors," J. Med. Chem. 37, 3090-3099 (1994).
Budavari, Susan (Editor), "The Merck Index" An Encylopedia of Chemicals, Drugs, and Biologicals; Merck & Co., Inc., p. 294 (1989).
Damewood, J. R., Jr. et al. "Nonpeptidic Inhibitors of Human Leukocyte Elastase. 2. Design, Synthesis, and in vitro Activity of a Series of 3-Amino-6-arylopyridin-2-one Trifluoromethyl Ketones," J. Med. Chem. 37, 3303-3312 (1994).
Skiles, J. W., et al. "Elastase Inhibitors Containing Conformationally Restricted Lactams as P.sub.3 -P.sub.2 Dipeptide Replacements," Bio. & Med. Chem. Ltrs. 3, 773-778 (1993).

Affiliated with

Also associated with

Rating

Serine protease inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Serine protease inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Serine protease inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-863495