Serine protease inhibitor--tripeptoid analogs

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

530330, 530331, A61K 3806, A61K 3807, C07K 5083, C07K 510

Patent

active

058078290

ABSTRACT:
The present invention relates to certain substituted oxadiazole, thiadiazole and triazole peptoids 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 24 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 Cyclooxypenase 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).
Wasseman, H.H., et al. "The Oxazole-Triamide Rearrangement. Application To Peptide Synthesis," Tet. Lett. vol. 23, No. 37, 3831-3834 (1982).
Comforth, 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).
Comforth, J. W., et al. "Synthesis of Oxazoles from Ethyl Acetoacetate. Ring-fission of Some Oxazoles-5-carboxylic Acids." J. Chem. Soc. 93-98 (1953).
Bemstein, 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).
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).
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)
Budavati, Susan (Editor), "The Merck Index" An Encyclopedia of Chemicals, Drugs, and Biologicals; Merck & Co., Inc., p. 294 (1989).

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Serine protease inhibitor--tripeptoid analogs 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 inhibitor--tripeptoid analogs, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Serine protease inhibitor--tripeptoid analogs will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-87026

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.