Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Tripeptides – e.g. – tripeptide thyroliberin – etc.
Patent
1995-03-13
1999-10-19
Tsang, Cecilia
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
Tripeptides, e.g., tripeptide thyroliberin , etc.
514 19, 514 18, 562575, A61K 3806
Patent
active
059691000
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.B 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: 4845079 (1989-07-01), Luly
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: 5221665 (1993-06-01), Skiles
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.
Siman et al., Proteolytic processing of .beta.-Amyloid precursor by calpain I, J. Neurosci. 10(7):2400-2411 (1990).
Almkvist et al., Cerebrospinal fluid levels of .alpha.-secretase-cleaved soluble amyloid precursor protein mirror cognition in a swedish family with Alzheimer disease and a Gene mutation, Arch. Neurol. 54:641-644 (1997).
Ito, 186081c Preparation of N-benzyloxycarbonyl tripeptide aldehydes for treatment of senile dementia, Chem. Abstr. 114(19):850 (1991).
Klafki et al., Calpain inhibitor I decreases .beta.A4 secretion from human embryonal kidney cells expressing .beta.-amyloid precursor protein carrying the APP670/671 double mutation, Neurosci. Lttrs 201:29-32 (1995).
Sarubbi et al., Peptide aldehydes as inhibitors of HIV protease, FEBS Lttrs 319(3):253-256, (1993).
Sasaki et al., Inhibitory effect of di-and tripeptidy 1 aldehydes on calpains and cathepsins, J. Enzyme Inhibition 3(3):195-200, (1990).
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).
Bradbury, et al., "1,2,4-Triazolo[4,3-.alpha.]pyrazine Derivatives with 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).
Cooper, et al., "X-ray Studies of Aspartic Proteinase-Statine Inhibitor Complexes," Biochemistry, 28:8596-8603 (1989).
Crawford, et al., "The design of peptidyldiazomethane inhibitors to distinguish between the cysteine proteinases calpain II, cathespin L and cathespin 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).
Fieser and Fieser, Reagents for Organic Synthesis, John Wiley and Sons, New York, 1:145.
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 (20S 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 y-trace alkaline microprotein--The basic defect in hereditary cerebral 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
Albrecht Elisabeth
McDonald Ian A.
Munoz Benito
Lukton David
Seidman Stephanie L.
SIBIA Neurosciences Inc.
Tsang Cecilia
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