Patents targeting γ-secretase inhibition and modulation for the treatment of Alzheimer's disease: 2004-2008

Expert Opinion on Therapeutic Patents

Volumn 18, Issue 7, 2008, Pages 693-703

  Garofalo, Albert W ^a  

^a ELAN PHARMACEUTICALS   (United States)

Author keywords

secrerase; Alzheimer's disease; Inhibitor; Modulator; North

Indexed keywords

4 CHLOROPHENYL THIOPHENE SULFONAMIDE; 5 CHLOROTHIOPHENE SULFONAMIDE; ACETIC ACID DERIVATIVE; AMINOTHIAZOLE MODERATOR; AMYLOID BETA PROTEIN; BENZODIAZEPINONE MALONAMIDE INHIBITOR; BENZOXAZEPINONE INHIBITOR; BIPHENYL CARBOXYLIC ACID MODULATOR; CAPROLACTAM DERIVATIVE; CARBAZOLE DERIVATIVE; CARBAZOLE MODULATOR; CARBOXYLIC ACID DERIVATIVE; E 2012; FLURBIPROFEN; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; IBUPROFEN; INDOMETACIN; ISOXAZOLE DERIVATIVE; N2 [2 (3,5 DIFLUOROPHENYL) 2 HYDROXYACETYL] N1 (6,7 DIHYDRO 5 METHYL 6 OXO 5H DIBENZ[B,D]AZEPIN 7 YL)ALANINAMIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PIPERIDIN 4 YL ACETIC ACID MODULATOR; PROTEINASE INHIBITOR; PYRAZOLE INHIBITOR; SULFONAMIDE; SULINDAC SULFIDE; TETRAHYDROQUINOLINE SULFONAMIDE; THIAZINE DERIVATIVE; THIAZOLE DERIVATIVE; UNINDEXED DRUG;

ALZHEIMER DISEASE; CLINICAL TRIAL; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENZYME ACTIVITY; ENZYME REGULATION; HUMAN; IC 50; NONHUMAN; PATENT; PROTEIN AGGREGATION; PROTEIN DEGRADATION; REVIEW;

EID: 48049097077     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543776.18.7.693     Document Type: Review

References (82)

1. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi M. Forecasting the global burden of Alzheimer's disease. Alzheimer Demen 2007;3:186-91
2. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112-7
3. Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992;256(5054):184-5
4. Roher AE, Lowenson JD, Clarke S, et al. β-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Nat Acad Sci USA 1993;90(22):10836-40
5. Kimberly WT, Lavoie MJ, Ostaszewski BL, et al. γ-Secretase is a membrane protein complex comprised of presenilin, nicastrin, aph-1, and pen-2. Proc Nat Acad Sci USA 2003;100(11):6382-7
6. Selkoe DJ, Wolfe MS. Presenilin: running with scissors in the membrane. Cell 2007;131:215-21
7. Wong GT, Manfra D, Poulet FM, et al. Chronic treatment with the γ-secretase inhibitor LY-411575 inhibits β-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem 2004;279(13):12876-82
8. Larner AJ. Secretases as therapeutic targets in Alzheimer's disease: patents 2000 - 2004. Expert Opin Ther Patents 2004;14(10):1403-20
9. Nguyen J-T, Yamani A, Kiso Y. Views on amyloid hypothesis and secretase inhibitors for treating Alzheimer's disease: progress and problems. Curr Pharm. Des 2006;12(33):4295-312
10. Olson RE, Marcin LR. Secretase inhibitors and modulators for the treatment of Alzheimer's disease. Ann Rep Med Chem 2007;42:27-47
11. Peretto I, La Porta E. γ-Secretase modulation and its promise for Alzheimer's disease: a medicinal chemistry perspective. Curr Top Med Chem 2008;81:38-46
12. Pissarnitski D. Advances in γ-secretase modulation. Curr Opin Drug Discov Dev 2007;10(4):392-402
13. Dovey HF, John V, Anderson JP, et al. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 2001;76(1):173-81
14. Schering Corp. WO03014075; 2003
15. Schering Corp. WO05028440; 2005
16. Schering Corp. WO04101562; 2004
17. Pissarnitski DA, Asberom T, Bara TA, et al. 2,6-Disubstituted N-arylsulfonyl piperidines as γ-secretase inhibitors. Bioorg Med Chem Lett 2007;17(3):57-62
18. Asberom T, Zhao Z, Bara TA, et al. Discovery of γ-secretase inhibitors efficacious in a transgenic animal model of Alzheimer's disease. Bioorg Med Chem Lett 2007;17(2):511-6
19. Josien H, Bara T, Rajagopalan M, et al. Small conformationally restricted piperidine N-arylsulfonamides as orally active γ-secretase inhibitors. Bioorg Med Chem Lett 2007;17(3):5330-5
20. Li H, Asberom T, Bara TA, et al. Discovery of 2,4,6-trisubstituted N-arylsulfonyl piperidines as γ-secretase inhibitors. Bioorg Med Chem Lett 2007;17(3):6290-4
21. Schering Corp. WO07084595; 2007
22. Wyeth-Arqule. WO03103660; 2003
23. Harrison B, Kreft A, Aschmies S, et al. Discovery of a novel series of Notch-sparing γ-secretase inhibitors [poster 99]. Presented at the 30th National Medicinal Chemistry Symposium; 2006 June; Seattle, WA
24. Wyeth. WO04092155; 2004
25. Wyeth. WO07098029; 2007
26. Wyeth. WO07098030; 2007
27. Wyeth. WO05073198; 2005
28. Resnick L, Sabalski J, Kreft A, et al. Discovery of novel heterocyclic sulfonamides as γ-secretase inhibitors [poster 110]. Presented at the 30th National Medicinal Chemistry Symposium; 2006 June; Seattle, WA
29. Bristol-Myers Squibb CO. WO05054180; 2005
30. Elan Pharmaceuticals, Inc. WO05090296; 2005
31. Elan Pharmaceuticals, Inc. WO07022502; 2007
32. Brigham E, Liao A, Bova M, et al. Treatment with a novel sulfonamide gamma-secretase inhibitor reduces beta-amyloid production without effects on Notch related toxicity in wildtype mice [poster 486.13]. Presented at Neuroscience; 2007 November; San Diego, CA
33. Basi G. APP substrate selective gamma-secretase inhibitors for treatment of Alzheimer's disease [presentation 13.5]. Presented at Neuroscience; 2007 November; San Diego, CA
34. Elan Pharmaceuticals, Inc. WO07064914; 2007
35. Elan Pharmaceuticals, Inc. WO07143523; 2007
36. Merck Sharp & Dohme Ltd. WO04039370; 2004
37. Merck Sharp & Dohme Ltd. WO04089911; 2004
38. Merck Sharp & Dohme Ltd. WO04101539; 2004
39. Shaw D, Best J, Dinnell K, et al. 3,4-Fused cyclohexyl sulfones as γ-secretase inhibitors. Bioorg Med Chem Lett 2006;16(11):3073-7
40. Merck Sharp & Dohme Ltd. WO06123183; 2006
41. Weng AP, Nam Y, Wolfe MS, et al. Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of Notch signaling. Mol Cell Biol 2003;23(2):655-64
42. Shih I-M, Wang T-L. Notch signaling, γ-secretase inhibitors, and cancer therapy. Cancer Res 2007;67(5):1879-82
43. Scott JP, Oliver SF, Brands KMJ, et al. Practical asymmetric synthesis of a γ-secretase inhibitor exploiting substrate-controlled intramolecular nitrile oxide-olefin cycloaddition. J Org Chem 2006;71(8):3086-92
44. F. Hoffmann-La Roche AG. WO07020190; 2007
45. Kitas EA, Galley G, Jakob-Roetne R, et al. Substituted 2-oxo-azepane derivatives are potent, orally active γ-secretase inhibitors. Bioorg Med Chem Lett 2008;18(1):304-8
46. Elan Pharmaceuticals, Inc. WO05042489; 2005
47. Elan Pharmaceuticals, Inc. WO06078753; 2006
48. Astrazeneca A.B. WO04080983; 2004
49. Neitzel ML, Marugg JL, Aubele DL, et al. Novel gamma secretase inhibitors showing potential for the treatment of Alzheimer's disease [poster P4-264]. Presented at the 10th International Conference on Alzheimer's Disease and Related Disorders; 2006 July; Madrid, Spain
50. F. Hoffmann-La Roche AG. WO06061136; 2006
51. F. Hoffmann-La Roche AG. WO08034735; 2008
52. Pfizer, Inc. WO04099200; 2004
53. Pfizer, Inc. WO05097114; 2005
54. Pfizer, Inc. WO07034326; 2007
55. Pfizer, Inc. WO05095334; 2005
56. Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology 1997;48(3):626-32
57. Anthony JC, Breitner JCS, Zandi PP, et al. Reduced prevalence of AD in users of NSAIDs and H2 receptor antagonists: The Cache County Study. Neurology 2000;54(11):2066-71
58. Weggen S, Eriksen JL, Das P, et al. A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity. Nature 2001;414(6860):212-6
59. Geerts H. Drug evaluation: (R)-flurbiprofen - an enantiomer of flurbiprofen for the treatment of Alzheimer's disease. IDrugs 2007;10(2):121-33
60. Matsuyama K, Sagiike H. Eisai shares fall after study on dementia drug halted (update 1). Available from: www.bloomberg.com/apps/ news?pid=20601202&sid=awsY3WA4uF7g&refer=healthcare [Last accessed 20 February, 2008]
61. Eisai to Resume Clinical Study to Evaluate E2012 as a Potential Next Generation Alzheimer's Disease Treatment. Available from: www.eisai.co.jp/enews/enews200818.html [Last accessed 19 April 19, 2008]
62. Neurogenetics, Inc. WO04110350; 2004
63. Eisai Co., Ltd. WO05115990; 2005
64. Eisai Co., Ltd. WO06046575; 2006
65. Eisai Co., Ltd. WO07135970; 2007
66. Eisai Co., Ltd. WO07135969; 2007
67. Merck Sharp & Dohme Ltd. WO05013985; 2005
68. Merck Sharp & Dohme Ltd. WO05108362; 2005
69. Merck Sharp & Dohme Ltd. WO05054193; 2005
70. Merck Sharp & Dohme Ltd. WO07116228; 2007
71. Merck Sharp & Dohme Ltd. WO07125364; 2007
72. Merck Sharp & Dohme Ltd. WO07110667; 2007
73. Merck Sharp & Dohme Ltd. WO06043064; 2006
74. Merck Sharp & Dohme Ltd. WO08030391; 2008
75. Cellzome AG. WO05110963; 2005
76. Cellzome AG. WO06021441; 2006
77. Cellzome AG. WO06045554; 2006
78. Ortho-Mcneil Pharmaceuticals, Inc. and Cellzome AG. WO07124394; 2007
79. Boehringer Ingelheim Pharma, Inc. WO05110422; 2005
80. Zhang Y-W, Wang R, Liu Q, et al. Presenilin/γ-secretase-dependent processing of β-amyloid precursor protein regulates EGF receptor expression. Proc Nat Acad Sci USA 2007;104(25):10613-8
81. Repetto E, Yoon I-S, Zheng H, Kang DE. Presenilin 1 regulates epidermal growth factor receptor turnover and signaling in the endosomal-lysosomal pathway. J Biol Chem 2007;282(43):31504-16
82. Jost M, Kari C, Rodeck U. The EGF receptor - an essential regulator of multiple epidermal functions. Eur J Dermatol 2000;10(7):505-10