Fluoro- and trifluoroalkyl-containing heterocyclic...

Details Fluoro- and trifluoroalkyl-containing heterocyclic... Fluoro- and trifluoroalkyl-containing heterocyclic...

2007-11-27

2007-11-27

Shameem, Golam M. M. (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

C549S029000, C549S062000, C549S065000, C514S438000

Reexamination Certificate

active

10810517

ABSTRACT:
Compounds of Formula (I),are provided where T is CHO, CON, or C(OH)R1R2; R1and R2are hydrogen, optionally substituted lower alkyl, CF3, optionally substituted alkenyl, or optionally substituted alkynyl; R3is hydrogen or optionally substituted lower alkyl; R4is (CF3)nalkyl, (CF3)n(substitutedalkyl), (CF3)nalkylphenyl, (CF3)nalkyl(substitutedphenyl), or (F)ncycloalkyl; n=1-3; R5is hydrogen, halogen, CF3, diene fused to Y when Y═C, or substituted diene fused to Y when Y═C; W, Y and Z are C, CR6or N where at least one of W, Y or Z are C; R6is hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO2, or NR7; R7is hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and R8is lower alkyl, CF3, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are also described.

REFERENCES:
patent: 5464853 (1995-11-01), Chan et al.
patent: 5514691 (1996-05-01), Chan et al.
patent: 5571821 (1996-11-01), Chan et al.
patent: 5591761 (1997-01-01), Chan et al.
patent: 5593846 (1997-01-01), Schenk
patent: 5594021 (1997-01-01), Chan et al.
patent: 5624937 (1997-04-01), Reel
patent: 5703129 (1997-12-01), Felsenstein
patent: 5852007 (1998-12-01), Chatterjee
patent: 5981168 (1999-11-01), Reiner
patent: 6248775 (2001-06-01), Vazquez
patent: 6376523 (2002-04-01), Chan et al.
patent: 6566536 (2003-05-01), Müller et al.
patent: 6610734 (2003-08-01), Kreft et al.
patent: 6657070 (2003-12-01), Resnick et al.
patent: 2003/0144531 (2003-07-01), Kreft et al.
patent: 2003/0229127 (2003-12-01), Kreft et al.
patent: 2004/0006050 (2004-01-01), Kreft et al.
patent: 510700 (1992-10-01), None
patent: 652009 (1995-05-01), None
patent: 1172361 (1999-12-01), None
patent: 1088821 (2001-04-01), None
patent: 5-148233 (1993-06-01), None
patent: 11-343279 (2002-01-01), None
patent: WO-95/29904 (1995-11-01), None
patent: WO-98/03166 (1998-01-01), None
patent: WO-98/22104 (1998-05-01), None
patent: WO-98/22493 (1998-05-01), None
patent: WO-00/09107 (2000-02-01), None
patent: WO-00/50391 (2000-08-01), None
patent: WO-01/23379 (2001-04-01), None
patent: WO-01/27091 (2001-04-01), None
patent: WO-01/27108 (2001-04-01), None
patent: WO-01/70677 (2001-09-01), None
patent: WO-02/057252 (2002-07-01), None
patent: WO-03/050062 (2003-06-01), None
patent: WO-03/050063 (2003-06-01), None
patent: WO-03/103660 (2003-12-01), None
A. Larner et al, “Review—Central & Peripheral Nervous Systems—Alzheimer's Disease: Towards Therapeutic Manipulation of the Amyloid Precursor Protein and Amyloid β-peptides”, Exp. Opin. Ther. Patents, 7(10):1115-1127 (1997).
C. Moore et al, “Inhibition of β-amyloid Formation as a Therapeutic Strategy”, Exp. Opin. Ther. Patents, 9(2):135-146 (1999).
V. John et al, “Alzheimer's Disease: Recent Advances on the Amyloid Hypothesis”, in Annual Reports in Medicinal Chemistry, Chapter 2, pp. 11-20 (1997).
G. Rishton et al, “Fenchylamine Sulfonamide Inhibitors of Amyloid β Peptide Production by the γ-Secretase Proteolytic Pathway: Potential Small-Molecule Therapeutic Agents for the Treatment of Alzheimer's Disease”, J. Med. Chem., 43(12):2297-2299 (Jun. 15, 2000).
B. Testa et al, “Prodrugs Revisited: The “Ad Hoc” Approach as a Complement to Ligand Design”, Medicinal Research Reviews, 16(3):233-241 (May 1996).
D. Skovronsky et al, “β-Secretase Revealed: Starting Gate for Race to Novel Therapies for Alzheimer's Disease”, TIPS, 21:161-163 (May 2000).
A. Ghosh et al, “Design of Potent Inhibitors for Human Brain Memapsin 2 (β-Secretase)”, J. Am. Chem. Soc., 122:3522-3523 (2000).
W. Esler et al, “Transition-State Analogue Inhibitors of γ-Secretase Bind Directly to Presenilin-1”, Nature Cell Biology, 2:428-434 (Jul. 2000).
Y-M. Li et al, “Photoactivated γ-Secretase Inhibitors Directed to the Active Site Covalently Label Presenilin 1”, Nature, 405:689-694 (Jun. 2000).
M. Wolfe et al, “A Substrate-Based Difluoro Ketone Selectively Inhibits Alzheimer's β-Secretase Activity”, J. Med. Chem., 41:6-9 (Jan. 1, 1998).
S. Sinha et al, “Purification and Cloning of Amyloid Precursor Protein β-Secretase from Human Brain”, Nature, 402:537-540 (Dec. 1999).
A. Goate, “Monogenetic Determinants of Alzheimer's Disease: APP Mutations”, CMLS Cell. Mol. Life Sci., 54:897-901 (Sep. 1998).
M. Sabbagh et al, “β-Amyloid and Treatment Opportunities for Alzheimer's Disease”, Alzheimer's Disease Review, 3:1-19 (1997).
C. Augelli-Szafran et al, β-Amyloid as a Target for Alzheimer's Disease Therapy, in Annual Reports in Medicinal Chemistry, Chapter 3, pp. 21-30 (1999).
J-C. Dodart et al, “The β-Amyloid Precursor Protein and its Derivatives: from Biology to Learning and Memory Processes”, Reviews in the Neurosciences, 11(2-3):75-93 (2000).
D. Small et al, “Alzheimer's Disease and the Amyloid β Protein: What is the Role of Amyloid?”, Journal of Neurochemistry, 73(2):443-449 (Aug. 1999).
J. Näslund et al, “Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline”, JAMA, 283(12):1571-1577 (Mar. 2000).
Q-X. Li et al, “The Amyloid Precursor Protein of Alzheimer Disease in Human Brain and Blood”, Journal of Leukocyte Biology, 66:567-574 (Oct. 1999).
S. Wagner et al, “Modulation of Amyloid β Protein Precursor Processing as a Means of Retarding Progression of Alzheimer's Disease”, The Journal of Clinical Investigation, 104(10):1329-1332 (Nov. 1999).
Y. Han et al, “Total Asymmetric Synthesis of Highly Constrained Amino Acids Isopropyl-2′, 6′-Dimethyl-Tyrosines”, Tetrahedron Letters, 38(29):5135-5138 (1997).
M. Findeis et al, “Modified-Peptide Inhibitors of Amyloid β-Peptide Polymerization”, Biochemistry, 38(21):6791-6800 (May 1999).
Roggo, “Inhibition of BACE, A Promising Approach to Alzheimer's Disease Therapy”, Curr. Top. Med. Chem., 2(4): 359-70 (Apr. 2002).
Tung et al., “Design of Substrate-Based Inhibitors of Human β-Secretase”, J. Med. Chem., 45(2):259-262 (2002).
Josien, “Recent Advances in the Development of Gamma-Secretase Inhibitors”, Curr. Opin. Drug. Discov. Devel., 5(4):513-25 (Jul. 2002).
Dovey et al., “Functional Gamma-Secretase Inhibitors Reduce Beta-Amyloid Peptide Levels in Brain”, J. Neurochem., 76:173-181 (Jan. 2001).
Olson et al., “Chapter 4. Secretase Inhibitors as Therapeutics for Alzheimer's Disease”, Ann. Reports in Med. Chem., 35:31 (2000).
Varghese et al., “Chapter 2. Alzheimer's Disease: Recent Advances on the Amyloid Hypothesis”, Ann. Reports Med. Chem., 32:11 (1997).
Abstract of Japanese Patent No. JP-11-343279, Jan. 26, 2002.
Wermuth et al., “Molecular variations based on isosteric replacements”, Prac. Med. Chem., Academic Press, pp. 203-237 (Feb. 1996).

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