Acylated enol derivatives as prodrugs of elastase inhibitors

Details Acylated enol derivatives as prodrugs of elastase inhibitors Acylated enol derivatives as prodrugs of elastase inhibitors

1996-06-25

1997-12-16

Dees, Jose G.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 19, 5142372, 514423, 548537, 560250, 560253, 544141, 530330, 530331, C07D 4312, C07K 5083, A61K 3806

Patent

active

056985231

ABSTRACT:
This invention relates to acylated enol derivatives of known elastase inhibitors. These compounds are useful in the treatment of various inflammatory diseases, including cystic fibrosis and emphysema or as prodrugs of compounds which are useful in the treatment of said diseases.

REFERENCES:
patent: 4277395 (1981-07-01), Bey et al.
patent: 4518528 (1985-05-01), Rasnick
patent: 4623639 (1986-11-01), Hassall
patent: 4629724 (1986-12-01), Ryone et al.
patent: 4636489 (1987-01-01), Seemuller et al.
patent: 4643991 (1987-02-01), Digenis et al.
patent: 4855303 (1989-08-01), Hoover
patent: 4873221 (1989-10-01), Trainor et al.
patent: 4880780 (1989-11-01), Trainor et al.
patent: 4910190 (1990-03-01), Bergeson et al.
patent: 4935405 (1990-06-01), Hoover et al.
patent: 5055450 (1991-10-01), Edwards et al.
patent: 5114927 (1992-05-01), Schirlin
patent: 5162307 (1992-11-01), Digenis et al.
patent: 5221665 (1993-06-01), Skiles
patent: 5478811 (1995-12-01), Peet et al.
patent: 5496927 (1996-03-01), Kolb et al.
patent: 5510333 (1996-04-01), Angelastro et al.
Skiles et al., J. Med. Chem. 1992, 35, pp. 641-662, "Inhibition of Human Leukocyte Elastase (HLE) by N-Substituted Peptidyl Trifluoromethyl Ketones.sup.1 ".
Skiles et al., J. Med. Chem. 1992, 35, pp. 4795-4808, "Inhibition of Human Leukocyte Elastase by N-Substituted Peptides Containing alpha", alpha-Difluorostatone Residues at P.sub.1.
Williams et al., publication, "Biologic Characterization of ICI 200,880 and ICI 200,355", Novel Inhibitors of Human Neutrophil Elastase 1,2 Am Rev. Respir. Dis. 1991, 144:875-883.
Kawase et al., Tetrahedron Letters, vol. 34, No. 5 pp. 859-862, 1993, "Unexpected Product from the Dakin-West Reaction of N-Acylprolines using Trifluoroacetic Anhydride: A Novel Access to 5-Trifluoromethyl-oxazoles".
Kawase, J. Chem. Soc., Chem. Commun., 1992, pp. 1076-1077, "Unusual Ring Expansion observed during the Dakin-West Reaction of Tetrahydroisoquinoline-1-carboxylic Acids using Trifluoroacetic Anhydride: an Expedient Synthesis of 3-Benzazepine Derivatives bearing a Trifluoromethyl Group".
Imperiali et al., "Inhibition of Serine Proteases by Peptidyl Flourumethyl Ketones," Biochemistry vol. 25, pp. 3760-3767 month not available (1986).
Skiles et al., "Inhibition of Human Leukocyte Elastase (HLE) by N-Substituted Peptidyl Trifluoromethyl Ketones," J. of Medicinal Chemistry, vol. 35, No. 4, pp. 641-662 month not available (1992).
Repine et al., "Renin Inhibitors Containing Esters at the P.sub.2 -Position. Oral Activity in a Derivative of Methyl Aminomalonate," J. Med. Chem. 34, pp. 1935-1943, month not available (1991).
Ueda et al., "The synthesis of arginylfluoroalkanes, their inhibition of trypsin and blood-coagulation serine proteinases and their anticoagulant activity," Biochem. J. 265, pp. 539-545, (1990).
Sham, H.L. et al., "Highly potent and specific inhibitors of human renin," FEBS Letters, vol. 220, No. 2, pp. 299-301, Aug. (1987).
Chemical Abstract Vo. 111, No. 9, Aug. 28, 1989, Lafuma et al. 111:70314q.
Powers et al, Chemical Abstracts, vol. 108:33954r, month not available 1988, Mechanism-based inhibitors of human leukocyte elastase.
Steinmeyer et al, Influence of Some Natural and Semisynthetic Agents on Elastase and Cathepsin G from Polymorphonuclear Granulocytes, Arzneim-Forsch/Drug Res. 41(l), Nr. month not available (1991), pp. 77-80.
McWherter et al, Novel Inhibitors of Human Leukocyte Elastase and Cathepsin G, Sequence Variants of Squash Seet Protease Inhibitor with Altered Protease Selectivity, Biochemistry month not available, 1989, 28, 5708-5713.
Reilly et al., The Degradation of Human Lung Elastin by Neutrophil Proteinases, Biochimica et Biophysica Acta, 621 month not available (1980) pp. 147-157.
Nakajima et al, Mapping the Extended Substrate Binding Site of Cathepsin G and Human Luekoocyte Elastase, The Journal of Biological Chemistry vol 254, No. 10, pp. 4027-4032, May 1979.
Rice et al, Regulation of Proteolysis at the Neutrophil-Substrate Interface by Secretory Leukoprotease Inhibitor, Science, vol. 249, pp. 178-181, Jul. 1990.
Travis, Structure, Function, and control of Neutrophil Proteinases, Jun. 24, 1988, The American Journal of Medicine, vol. 84 (Suppl 6A) pp. 37-42.
Powers, J.C., Eleventh American Peptide Syposium, Abstracts, The Salk Institute and U. of CA, San Diego (1989). Internal notes taken at meeting.
Travis, J. et al., "Potential Problems in Designing Elastase Inhibitors for Therapy," Am Rev Respir Dis, Pulmonary Perspective, vol. 143 pp. 1412-1415 month not available 1991.
Petrillo, E.W., et al., Chapter 6. Antihypertensive Agents, Section II. Cardiovascular and Pulmonary Agents, Annual Reports in Medicinal Chemistry, 25, month not available 1989, Academic Press, Inc., D.W. Robertson Editor.
Chemical Abstract vol. 111, No. 21, Nov. 20, 1989, Galzigna et al. 111:190/312.
Angelastro et al, "An Efficient Synthesis of Novel a-Diketone and A-Keto Ester Derivatives of N-Protected Amino Acids and Peptides" J. Org. Chem. 54, pp. 3913-3916 month not available (1989).
Angelastro et al, "Inhibition of Human Neurtophil Elastase with Peptidyl Electrophilic Ketones. 2. Orally Active P.sub.G -Val-Pro-Val-Pentafluoroethyl Ketones" Journal of Medicinal Chemistry, 37 month not available (1994).
Angelastro et al., "Janus Compounds: Dual Inhibitors of Proteinases" Bioorganic & Medicinal Chemistry Letters, vol. 3, No. 4, pp. 525-530 month not available (1993).
Mehdi, "Synthetic and Naturally Occurring Protease Inhibitors Containing an Electrophilic Carbonyl Group." Bioorganic Chemistry, 21, pp. 249-259 month not available (1993).
Angelastro et al., "Efficient Preparation of Peptidyl Pentafluoroethyl Ketones" Tetrahedron Letters, vol. 33, No. 23, pp. 3265-3268 month not available (1992).
Burkhart, et al, "A Novel Method for the Preparation of Peptidyl a-Keto Esters" Tetrahedron Letters, vol. 31, No. 10, pp. 1385-1388 month not available (1990).
Peet et al, Synthesis of Peptidyl Fuuoromethyl Ketones and Peptidyl .alpha.-Keto Esters as Inhibitors of Procine Pancreatic Elastase, Human Neutrophil Elastase, and Rat and Human Neutrophil Cathepsin G,J. Med Chem, month not available 1990, 33, pp. 394-407.
Doherty et al, Novel Inhibitors of Polymorphonuclear Neutrophil (PMN) Elastase and Cathepsin G: Evaluation in vitro of their potential for the Treatment of inflammatory connective tissue damage, Int. J. Immunopharmac, vol. 12, No. 7, pp. 787-795, month not available 1990.
Mehdi et al, The inhibition of human Neutrophil elastase and cathepsin G by Peptidyl 1,2-dicarbonyl derivatives, Biochemical and Biophysical Research Communications, vol. 166, No. 2, Jan. 1990, pp. 595-600.
Shah et al., Orally Active .beta.-Lactam Inhibitors of Human Leukocyte Elastase-1. J. Med Chem, 35, pp. 3745-3754 month not available (1992).
Snider, Experimental Studies on Emphysema and Chronic Bronchial Injury, Eur. J. Respir Dis month not available (1986) 69 (Suppl. 146) pp. 17-35.
Malech et al, Current Concepts: Immunology Neutrophils in Human Diseases, Medical Intelligence-vol. 317. No. 11, Sep. 1987.
Fletcher et al, A comparison of .alpha..sub.1 -Proteinase Inhibitor Methoxysuccinyl-ala-ala-pro-val-chloromethylketone and Specific .beta.-Lactam Inhibitors in a accute Model of Human Polymorphonuclear Leukocyte Elastase-induced Lung Hemorrhage in the hamster, Am Rev Respir Dis month not available 990; 141:672-677.
Hassall et al, A new class of inhibitors of human leucocyte elastase, FEBS 2444, vol. 183, No. 2, Apr. 1985.
Bundgaard, Hans, "Design of Bioreversible Drug Derivatives and the Utility of the Double Prodrug Concept", Bioreversible Carriers In Drug Design, 1987 pp. 13, 63-65.
Imperiali et al, Biochemistry, vol. 21, pp. 3760-3767 (1986).
Powers, J.C., Eleventh American Peptide Symposium, Abstracts, The Salk Institute and U. of CA, San Diego (1989). Internal Notes taken at meeting.
Angelastro et al, Bioorganic & Medicinal Chemistry Letters, vol. 2, No 10, pp. 1235-1238 (1992).
J. Med. Chem. 33, pp. 11-13 (1990) "Communications to the Editor".
Copeland, T.D. et al, Biochem. Biophys. Res. Commun,. vol. 169., No. 1, pp. 310-314 (1990

Affiliated with

Also associated with

Rating

Acylated enol derivatives as prodrugs of elastase 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 Acylated enol derivatives as prodrugs of elastase inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Acylated enol derivatives as prodrugs of elastase inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-206019