Aspartyl protease inhibitors

Details Aspartyl protease inhibitors Aspartyl protease inhibitors

2006-10-03

2006-10-03

Lambkin, Deborah C. (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C549S076000, C549S077000

Reexamination Certificate

active

07115652

ABSTRACT:
The present invention provides compounds having the formula:wherein R1, R′, R2, R3, R3′, R4, X1, X2and X3are as defined herein, and pharmaceutical compositions thereof. The present invention also provides methods of inhibiting proteases, more specifically aspartyl proteases. In certain embodiments, compounds inhibit BACE (β-site APP-cleaving enzyme), and thus are useful in the treatment or prevention of a disease characterized by β-amyloid deposits in the brain (including, but not limited to, Alzheimer's Disease). The present invention also provides methods for preparing compounds of the invention.

REFERENCES:
patent: 5196438 (1993-03-01), Martin et al.
patent: 5413999 (1995-05-01), Vacca et al.
patent: 5585397 (1996-12-01), Tung et al.
patent: 5728718 (1998-03-01), Randad et al.
patent: 634756 (1993-04-01), None
patent: 0 316 965 (1989-05-01), None
patent: 0 356 223 (1990-02-01), None
patent: 0 386 611 (1990-09-01), None
patent: WO 93/02674 (1993-02-01), None
patent: WO 98/46599 (1998-10-01), None
patent: WO 00/56335 (2000-03-01), None
patent: WO 00/40558 (2000-07-01), None
patent: WO 02/02505 (2002-01-01), None
*Ajay, et al., “Designing Libraries with CNS Activity”,J. Med. Chem., 42:4942-4951, 1999.
Bro{hacek over (z)}ková, et al., “Peptidomimetic Inhibitors of Extracellular Aspartic Proteinases ofCandida albicansANDCandida trooicalis”, Collect. Czech. Chem. Commun., 64:130-137, 1999.
*Ermolieff, et al., “Proteolytic Activation of Recombinant Pro-Memapsin 2 (Pro-β-secretase) Studied with New Fluorogenic Substrates”,Biochemistry, 39:12450-12456, 2000.
*Haque, et al., “Potent, Low-Molecular-Weight Non-Peptide Inhibitors of Malarial Aspartyl Protease Plasmepsin II”,J. Med. Chem., 42: 1428-1440, 1999.
Herrero, et al. “C-Backbone ranches peptides via reductive amination of cyanomethyleneamino pseudopeptides”, Tetrahedron Letters, 43: 1421-1424, 2002.
*Hussain, et al., “Identification of a Novel Aspartic Protease (Asp 2) as β-Secretase”,Mol. Cell. Neurosci., 14:419-427, 1999.
*Sabbagh, et al., “β-Amyloid and Treatment Opportunities for Alzheimer's Disease”,Alz. Dis. Rev., 3:1-19, 1997.
*Sinha, et al., “Purification and cloning of amyloid precursor protein β-secretase from human brain”,Nature, 402:537-540, 1999.
Suárez-Gea, et al., “Branches Peptides and Conformationally Constrained Analogues form Cyanomethyleneamino Pseudopeptides”, Tetrahedron Letters, 37:2083-2084, 1996.
*Vassar, et al., “β-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by Transmembrane Aspartic Protease BACE”,Science, 286:735-741, 1999.
Wolfe, et al., “A Substrate-Based Difluoro Ketone Selectively Inhibits Alzheimer's γ-Secretase Activity”, J. Med. Chem., 41:6-9, 1998.
*Yan, et al., Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity,Nature, 402:533-537, 1999.
International Search Report issued for PCT application PCT/US03/18858.

Affiliated with

Also associated with

Rating

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

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3674722