Methods of treating neurodegenerative disorders using protease i

Details Methods of treating neurodegenerative disorders using protease i Methods of treating neurodegenerative disorders using protease i

1995-05-18

1999-02-16

Tsang, Cecilia J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 18, 530331, 562575, 562562, 562445, 562567, A61K 3805

Patent

active

058721010

ABSTRACT:
Methods of use of compounds and compounds for the treatment of disorders characterized by the cerebral deposition of amyloid are provided. Among the compounds are those of formulae (I), (II) and (III): ##STR1## in which R.sub.1 is preferably 2-methyl propene, 2-butene, norleucine; R.sub.2, R.sub.4, and R.sub.8 are each independently methyl or ethyl; R.sub.3 is preferably iso-butyl or phenyl; R.sub.5 is preferably iso-butyl; R.sub.6 is H or methyl; R.sub.7 --(Q).sub.n is preferably benzyloxycarbonyl or acetyl; Q is preferably --C(O)--; R.sub.8 is preferbly iso-butyl; R.sub.A =--(T).sub.m --(D).sub.m --R.sub.1, is which T is preferably oxygen or carbon, and D is preferably a mono-unsaturated C.sub.3-4 alkenyl being more preferred; and X is an alcohol, particularly a secondary alcohol.

REFERENCES:
patent: 4044126 (1977-08-01), Cook et al.
patent: 4364923 (1982-12-01), Cook et al.
patent: 4414209 (1983-11-01), Cook et al.
patent: 4472305 (1984-09-01), Hansen et al.
patent: 4666829 (1987-05-01), Glenner et al.
patent: 4701407 (1987-10-01), Appel
patent: 4840935 (1989-06-01), Wagnon et al.
patent: 5015570 (1991-05-01), Scangos et al.
patent: 5034376 (1991-07-01), Hoover
patent: 5039511 (1991-08-01), Quay et al.
patent: 5039642 (1991-08-01), Chrobaczek et al.
patent: 5081284 (1992-01-01), Higuchi et al.
patent: 5200339 (1993-04-01), Abraham
patent: 5213962 (1993-05-01), van Nostrandt et al.
patent: 5218100 (1993-06-01), Muller-Hill et al.
patent: 5223633 (1993-06-01), Hoppe et al.
patent: 5231000 (1993-07-01), Majocha et al.
patent: 5242932 (1993-09-01), Gandy et al.
patent: 5270165 (1993-12-01), van Nostrandt et al.
patent: 5284828 (1994-02-01), Hemmi et al.
patent: 5374623 (1994-12-01), Zimmerman et al.
patent: 5427931 (1995-06-01), Van Nostrand et al.
patent: 5430022 (1995-07-01), Hemmi et al.
patent: 5470833 (1995-11-01), Ishikawa et al.
patent: 5496928 (1996-03-01), Ishikawa et al.
patent: 5538845 (1996-07-01), Knops et al.
patent: 5547841 (1996-08-01), Marrotta et al.
patent: 5593846 (1997-01-01), Schenk et al.
patent: 5604102 (1997-02-01), McConlogue et al.
patent: 5605811 (1997-02-01), Seubert et al.
patent: 5612486 (1997-03-01), McConlogue et al.
patent: 5652092 (1997-07-01), Vitek et al.
patent: 5656477 (1997-08-01), Vitek et al.
patent: 5703209 (1997-12-01), Vitek et al.
patent: 5766846 (1998-06-01), Schlossmacher et al.
Angelastro, et al., "Inhibition of Human Neutrophil Elastase with Peptidyl Electrophilic Ketones," J. Med. Chem., 37:4538-4554 (1994).
Angliker, et al., "Inactivation of calpain by peptidyl fluoromethyl ketones," J. Med. Chem., 35:216-220 (1992).
Arner, et al., "1-Chloro-2,4-dinitrobenzene is an Irreversible Inhibitor of Human Thioredoxin Reductase," J. Biol. Chem., 270(8):3479-3482 (1995).
Bodanszky and Bodanszky, "I. Protecting Groups 5. The tert.Butyloxycarbonyl (Boc) Group," The Practice of Peptide Synthesis, Springer-Verlag, pp. 18-20 (1984). Human Renin Inhibitory Activity," J. Med. Chem., 33:2335-2342 (1990).
Breaux and Bender, "The binding of specific and non-specific aldehyde substrate analogs to .alpha.-chymotrypsin," FEBS Letters, 56(1):81-84 (1975).
Buxbaum, et al., "Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer .beta./A4 amyloid protein precursor, " Proc. Natl. Acad. Sci. USA, 89:10075-10078 (1992).
Cai, et al., "Release of excess amyloid .beta. protein from a mutant amyloid .beta. protein precursor," Science, 259:514-516 (1993).
Caporaso, et al., "Chloroquine inhibits intracellular degradation but not secretion of Alzheimer .beta./A4 amyloid precursor protein," Proc. Natl. Acad. Sci. USA, 89:2252-2256 (1992).
Citron, et al., "Mutation of the .beta.-amyloid precursor protein in familial Alzheimer's disease increases .beta.-protein production," Nature, 360:672-674 (1992).
Cooper, et al., "X-ray Crystallographic Analysis of Inhibition of Endothiapepsin by Cyclohexyl Renin Inhibitors," Biochemistry, 31:8142-8150 (1992).
Crawford, et al., "The design of peptidyldiazomethane inhibitors to distinguish between the cysteine proteinases calpain II, cathepsin L and cathepsin B," J. Biochem., 253:751-758 (1988).
Crawford, "Protein and peptide inhibitors of calpains," Intracellular Calcium-Dependent Proteolysis, Chapter 5, pp. 75-89.
Davis, et al., "A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease," New England J. of Med., 327(18):1253-1259 (1992).
De Strooper, et al., "Basolateral Secretion of Amyloid Precursor Protein in Madin-Darby Canine Kidney Cells is Disturbed by Alterations of Intracellular pH and by Introducing a Mutation Associated with Familial Alzheimer's Disease," J. Biol. Chem., 270(8):4058-4065 (1995).
Dess and Martin, "Readily accessible 12-I-5.sup.1 oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones," J. Org. Chem., 48:4155-4156 (1983).
Dolle, et al., "Aspartyl .alpha.-((1-Phenyl-3-(trifluoromethyl)-pyrazol-5-yl)oxy)methyl Ketones as Interleukin-1.beta. Converting Enzyme Inhibitors. Significance of the P.sub.1 and P.sub.3 Amido Nitrogens for Enzyme-Peptide Inhibitor Binding," J. Med. Chem., 37(23):3863-3866 (1994).
Esch, et al., "Cleavage of amyloid .beta. peptide during constitutive processing of its precursor," Science, 24:1122-1124 (1990).
Farlow, et al., "Low cerebrospinal-fluid concentrations of soluble amyloid .beta.-protein precursor in hereditary Alzheimer's disease," Lancet, 340:453-454 (1992).
Figueiredo-Pereira, et al., "Comparison of the effect of calpain inhibitors on two extralysosomal proteinases: The multicatalytic proteinase complex and m-calpain," J. Neurochemistry, 62(5):1989-1994 (1994).
Figueiredo-Pereira, et al., "A new inhibitor of the chymotrypsin-like activity of the multicatalytic proteinase complex (2OS proteasome) induces accumulation of ubiquitin-protein conjugates in a neuronal cell," J. Neurochemistry, 63(4):1578-1581 (1994).
Folstein, et al., "Mini-mental state"--A practical method for grading the cognitive state of patients for the clinician, J. Psychiat. Res., 12:189-198 (1975).
Francis, et al., "Soluble .beta.-amyloid precursor protein and pyramidal neuron loss," Lancet, 341:431 (1993).
Gisin, "The preparation of Merrifield-resins through total esterification with cesium salts," Helvetica Chimica Acta, 56(5):1476-1482 (1973).
Glenner and Wong, "Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein," Biochem. and Biophys. Res. Comm., 120(3):885-890 (1984).
Grubb, et al., "Abnormal metabolism of .gamma.-trace alkaline microprotein--The basic defect in hereditary cerebal hemorrhage with amyloidosis," N. England J. of Med., 311(24):1547-1549 (1984).
Haas, et al., "Targeting of cell-surface .beta.-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments," Nature, 357:500-503 (1992).
Hardy, "The genetics of Alzheimer's disease," Neurosci. Facts, 3:65 (1992).
Hardy and Higgins, "Alzheimer's disease: The amyloid cascade hypothesis," Science, 256:184-185 (1992).
Harris, et al., "Characterization of a Continuous Fluorogenic Assay for Calpain L. Kinetic Evaluation of Peptide Aldehydes, Halomethyl Ketones and (Acyloxy)Methyl Ketones as Inhibitors of the Enzyme," Bioorg. & Med. Chem. Lett., 5(4):393-398 (1995).
Henrikkson, et al., "Analysis and quantitation of the .beta.-amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients with a monoclonal antibody-based immunoassay," J. Neurochem., 56(3):1037-1042 (1991).
Imperiali and Abeles, "Inhibition of Serine Proteases by Peptidyl Fluoromethyl Ketones," Biochemistry, 25:3760-3767 (1985).
Inoue, et al., "Inhibition of degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in Vivo by cysteine protease inhibitors," J. Biol. Chem., 266(20):13311-13317 (1991).
Inoue, et al., "Cellular detoxification of tripeptidyl aldehydes by an aldo-keto reductase," J. Biol. Chem., 268(8):5894-5898 (1993).
Ito, et al., "Synthetic study of peptide aldehydes," Chem. Pharm. Bull., 23(12):3106-3113 (1975).
Ito, et al., "Peptide aldehydes inhi

Affiliated with

Also associated with

Rating

Methods of treating neurodegenerative disorders using protease i does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods of treating neurodegenerative disorders using protease i, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of treating neurodegenerative disorders using protease i will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2062620