Fluoro- and trifluoroalkyl-containing heterocyclic...

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

2007-06-15

2009-06-16

Shameem, Golam 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

07547725

ABSTRACT:
Compounds of Formula (I),are provided where T is CHO, COR8, 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(substituted alkyl), (CF3)nalkylphenyl, (CF3)nalkyl(substituted phenyl), 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), Vasquez
patent: 6376523 (2002-04-01), Chan et al.
patent: 6566536 (2003-05-01), Muller et al.
patent: 6610734 (2003-08-01), Kreft et al.
patent: 6657070 (2003-12-01), Resnick
patent: 6800764 (2004-10-01), Kreft et al.
patent: 6878742 (2005-04-01), Kreft et al.
patent: 7166622 (2007-01-01), Kreft et al.
patent: 7300951 (2007-11-01), Kreft et al.
patent: 2004/0198778 (2004-10-01), Kreft et al.
patent: 2005/0171180 (2005-08-01), Resnick et al.
patent: 2005/0196813 (2005-09-01), Kreft et al.
patent: 2007/0037778 (2007-02-01), 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-03/050063 (2003-06-01), None
patent: WO-03/103660 (2003-12-01), None
patent: WO-2005/073198 (2005-08-01), None
Abstract of Japanese Patent No. JP-11-343279 Jan. 26, 2002.
Augelli-Szafran et al., “β-amyloid as a target for Alzheimer's Disease therapy”, Annual Reports in Medicinal Chemistry, Ch. 3:21-30, 1999.
Dodart et al., “The β-amyloid precursor protein and its derivatives: From biology to learning and memory process”, Reviews in the Neurosciences, 11(2-3):75-93, 2000.
Dovey et al., “Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain”, J. Neurochem., 76:173-181, Jan. 2001.
Esler et al., “Transition-state analogue inhibitors of β-secretase bind directly to presenilin-1”, Nature Cell Bio., 2:428-434, Jul. 2000.
Findeis et al., “Modified-peptide inhibitors of amyloid β-peptide polymerization”, Biochem., 38(21):6791-6800, May 1999.
Ghosh et al., “Design of potent inhibitors for human brain memapsin 2 (β-secretase)”, J. Am. Chem. Soc., 122:3522-3523, 2000.
Goate, A., “Monogenetic determinants of Alzheimer's Disease: APP mutations”, Cell. Mol. Life Sci., 54:897-901, Sep. 1998.
Han et al., “Total asymmetric synthesis of highly constrained amino acids isopropyl-2′,6′-dimethyl-tyrosines”, Tetrahedron Letters, 38(29):5135-5138, 1997.
John et al., “Chapter 2. Alzheimer's Disease: Recent advances on the amyloid hypothesis”, Ann. Reports Med. Chem., 32:11-20, 1997.
Josien, H., “Recent advances in the development of gamma-secretase inhibitors”, Curr. Opin. Drug. Discov. Devel., 5(4):513-525, Jul. 2002.
Larner et al., “Review—Central and peripheral nervous systems—Alzheimer's disease: Towards therapeutic manipulation of the amyloid precursor protein and amyloid peptides”, Exp. Opin. Ther. Patents, 7(10):1115-1127, 1997.
Li et al., “Photoactivated β-secretase inhibitors directed to the active site covalently label presenilin 1”, Nature, 405:689-694, Jun. 2000.
Li et al., “The amyloid precursor protein of Alzheimer's Disease in human brain and blood”, J. of Leuko. Bio., 66:567-574, Oct. 1999.
Moore et al., “Inhibition of β-amyloid formation as a therapeutic strategy”, Exp. Opin. Ther. Patents, 9(2):135-146, 1999.
Näslund et al., “Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline”, JAMA, 283(12):1571-1577, Mar. 2000.
Olson et al., “Chapter 4. Secretase inhibitors as therapeutics for Alzheimer's Disease”, Ann. Reports in Med. Chem., 35:31, 2000.
Rishton et al., “Fenchylamine sulfonamide inhibitors of amyloid peptide production by the β-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.
Roggo, S., “Inhibition of BACE, A promising approach to Alzheimer's Disease therapy”, Curr. Top. Med. Chem., 2(4):359-370, Apr. 2002.
Sabbagh et al., “β-amyloid and treatment opportunities for Alzheimer's Disease”, Alzheimer's Disease Review, 3:1-19, 1997.
Sinha et al., “Purification and cloning of amyloid precursor protein β-secretase from human brain”, Nature, 402:537-540, Dec. 1999.
Skovronsky et al., “β-secretase revealed: Starting gate for race to novel therapies for Alzheimer's Disease”, TIPS, 21:161-163, May 2000.
Small et al., “Alzheimer's Disease and the amyloid protein: What is the role of amyloid?”, J. of Neurochem., 73(2):443-449, Aug. 1999.
Testa et al., “Prodrugs revisited: The “Ad Hoc” approach as a complement to ligand design”, Med. Res. Rev., 16(3):233-241, May 1996.
Tung et al., “Design of substrate-based inhibitors of human β-secretase”, J. Med. Chem., 45(2):259-262, 2002.
Varghese et al., “Chapter 2. Alzheimer's Disease: Recent Advances on the Amyloid Hypothesis”, Ann. Reports Med. Chem., 32:11, 1997.
Wagner et al., “Modulation of amyloid protein precursor processing as a means of retarding progression of Alzheimer's Disease”, J. Clin. Invest., 104(10):1329-1332, Nov. 1999.
Wermuth et al., “Molecular variations based on Isosteric replacements”, The Prac. of Med. Chem., 203-237, 1996.
Wolfe et al., “A substrate-based difluoro ketone selectively inhibits Alzheimer's β-secretase activity”, J. Med. Chem., 41:6-9, Jan. 1, 1998.

Affiliated with

Also associated with

Rating

Fluoro- and trifluoroalkyl-containing heterocyclic... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Fluoro- and trifluoroalkyl-containing heterocyclic..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Fluoro- and trifluoroalkyl-containing heterocyclic... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-4146687