Peptide and peptide analog protease inhibitors

Details Peptide and peptide analog protease inhibitors Peptide and peptide analog protease inhibitors

1995-05-17

1999-10-05

Tsang, Cecilia J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 18, 530331, 562575, A61K 3805

Patent

active

059624191

ABSTRACT:
Methods of use of compounds for the treatment of disorders characterized by the cerebral deposition of amyloid are provided. Among the compounds provided for use in the methods are those of the formula: ##STR1## in which R.sub.1 is preferably 2-methylpropenyl, 2-butenyl, cyclohexyl or cyclohexylmethyl; R.sub.2, R.sub.4, and R.sub.8 are each preferably independently methyl or ethyl; R.sub.3 is preferably iso-butyl or phenyl; Q is preferably --C(O)--; R.sub.B is preferably iso-butyl; R.sub.A is --(T).sub.m --(D).sub.m --R.sub.1, in which T is preferably oxygen or NH, m is 0 or 1, and D is preferably C.sub.1-4 alkyl or C.sub.2-4 alkenyl; and X is preferably an aldehyde, .alpha.-ketoester or .alpha.-ketoamide.

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 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: 5081284 (1992-01-01), Higuchi et al.
patent: 5164371 (1992-11-01), Edwards 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: 5232928 (1993-08-01), Skiles
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: 5348963 (1994-09-01), Gandy 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: 5436229 (1995-07-01), Ruterbories et al.
patent: 5441870 (1995-08-01), Seubert et al.
patent: 5470833 (1995-11-01), Ishikawa et al.
patent: 5496928 (1996-03-01), Ishikawa et al.
patent: 5508167 (1996-04-01), Roses et al.
patent: 5538845 (1996-07-01), Knops et al.
patent: 5547841 (1996-08-01), Marrotta et al.
patent: 5578451 (1996-11-01), Nishimoto
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: 5631168 (1997-05-01), Growdon et al.
patent: 5643726 (1997-07-01), Tanzi 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.
patent: 5797853 (1998-08-01), Musha et al.
Cooper, et al., "X-ray Studies of Aspartic Proteinase-Statine Inhibitor Complexes," Biochemistry, 28:8596-8603 (1989).
O'Donnell, et al., "Synthesis of .beta.,.gamma.-Unsaturated Amino Acid Derivatives by Alkyne Carbometalation-Palladium Catalyzed Coupling with 2-Aza-.pi.-Allyl Palladium Complexes," Tetrahedron Letters, 35(50):9383-9386 (1994).
Ocain and Rich, ".alpha.-keto amide inhibitors of aminopeptidases," J. Med. Chem., 35:451-456 (1992).
Van Nostrandt, et al., "Immunopurification and protease inhibitory properties of protease nexin-2/amyloid .beta.-protein precursor," J. Biol. Chem., 265(17): 9591-9594 (1990).
Higgins, et al., "Early Alzheimer disease-like histopathology increases in frequency with age in mice transgenic for .beta.-APP751," Proc. Natl. Acad. Sci. USA, 92:4402-4406 (1995).
Borman, "Diverse strategies emerge for diagnosing Alzheimer's disease", C&EN, pp. 33-34 (1996).
de Lustig et al., "Peripheral markers and diagnostics criteria in Alzheimer's disease: Critical evaluations", Rev. Neurosci. 5:213-225 (1994).
Dresse et al., "Towards a pharmacological approach of alzheimer's disease based on the molecular biology of the amyloid precursor protein (APP)", Life Sci 35(25/26):2179-2187 (1994).
English language Abstract of Japanese Patent No. 6345722 (Dialog(R)File 351:Derwent WPI Accession No.: 95-070275).
Kazmaier, "Introduction of Allylic Side Chains onto Peptides by Pd(O)-Catalyzed "Ester Enolate Claisen Rearrangement"" J. Org. Chem.59:6667 (1994).
Price et al., "Alzheimer disease and the prion disorders amyloid .beta.-protein and prion protein amyloidoses", Proc. Natl. Acad. Sci. USA 90:6381-6384 (1993).
Selkoe, "Normal and abnormal biology of the .beta.-amyloid precursor protein", Annu. Rev. Neurosci. 17:489-517 (1994).
Sham et al., "Highly potent and specific inhibitors of human renin", FEB 220(2):299-301 (1987).
Sisodia et al., "Cellular and molecular biology of alzheimer's disease and animal models", Neurodegenerative Diseases 5(1):59-68 (1995).
Smith and Anderson, "The molecular pathology of Alzheimer's disease: are we any closer to understanding the neurodegenerative process?" Neuropathol. Appl. Neurobiol. 20(4):322-338 (1994).
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).
Siman et al., Proteolytic processing of .beta.-Amyloid precursor by calpain I, J. Neurosci. 10(7):2400-2411 (1990).
Anderson et al, "Differential induction of immediate early gene proteins in cultured neurons by .beta.-amyloid (A.beta.): Association of c-jun with A.beta.-induced apoptosis," J. Neurochem. 65 (4):1487-1498 (1995).
Asami-Odaka et al., "Long amyloid .beta.-protein secreted from wild-type human neuroblastoma IMR-32 cells," Biochemistry 34:10272-10278 (1995).
Barry et al., "Protection against mycoplasma infection using expression-library immunization," Nature 377:632-635 (1995).
Checler, "Processing of the .beta.-amyloid precursor protein and its regulation in Alzheimer's disease," J. Neurochem. 65(4):1431-1444 (1995).
Le et al, ".beta.-amyloid.sub.1-40 increases expression of .beta.-amyloid precursor protein in neuronal hybrid cells," J. Neurochem. 65(5):2373-2376 (1995).
Mahdi et al., "Protease nexin/amyloid .beta.-protein precursor inhibits factor Xa in the prothrombinase complex," J. Biol. Chem. 270(40):23468-23474 (1995).
Mark et al., "Amyloid .beta.-peptide impairs ion-motive ATPase activities: Evidence for a role in loss of neuronal Ca.sup.2+ homeostasis and cell death," J. Neurosci. 15(9):6239-6249 (1995).
Moss et al., "Peptidometric inhibitors of herpes simplex virus ribonucleotide reductase: A new class of antiviral agents," J. Med. Chem. 38:3617-3623 (1995).
Pike et al., "Amino-terminal deletions enhance aggregation of .beta.-amyloid peptides in vitro," J. Biol. Chem. 270(41):23895-23898 (1995).
Thaisrivongs et al., "Structure-based design of novel HIV protease inhibitors: Carboxamide-containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent nonpeptidic inhibitors," J. Med. Chem. 38:3624-3637 (1995).
Wang et al., "A novel matrix attachment region DNA binding motif identified using a random phage peptide library," J. Biol. Chem. 270(40):23239-23242 (1995).
Xu et al., "Regulated formation of Golgi secretory vesicles containing Alzheimer's .beta.-amyloid precursor protein," J. Biol. Chem. 270(40):23243-23245 (1995).
Yoshimoto et al., "NACP, the precursor protein of the non-amyloid .beta./A4 protein (A.beta.) component of Alzheimer's disease amyloid, binds A.beta. and stimulates A.beta. aggregation," Proc. Natl. Acad. Sci. USA 92:9141-9145 (1995).
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 bind

Affiliated with

Also associated with

Rating

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

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1171454