Modulators and inhibitors of γ- and β-secretases

Neurodegenerative Diseases

Volumn 3, Issue 4-5, 2006, Pages 290-297

  Schmidt, Boris ^a   Baumann, Stefanie ^a   Narlawar, Rajeshwar ^a   Braun, Hannes A ^a   Larbig, Gregor ^a  

^a DARMSTADT UNIVERSITY OF TECHNOLOGY   (Germany)

Author keywords

Alzheimer's disease; Aspartic protease; BACE inhibitors; Presenilin; Secretase

Indexed keywords

AMYLOID PRECURSOR PROTEIN; BETA SECRETASE; BETA SECRETASE INHIBITOR; BMS 299897; BSC 2805; BSC 2901; BSC 2912; BSC 2933; BSC 3009; BSC 3040; BSC 3092; BSC 3552; BSC 3553; BSC 3554; CYCLOOXYGENASE 1 INHIBITOR; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; IBUPROFEN; IMATINIB; INDOMETACIN; L 658 458; LY 3474973; LY 374973; LY 411575; NAPROXEN; OM00 3; OM99 2; SULINDAC; UNCLASSIFIED DRUG; UNINDEXED DRUG; WO 05013985; WO 2003072535; WO 2004014843;

ALZHEIMER DISEASE; CONFERENCE PAPER; DRUG MECHANISM; ENZYME INHIBITION; ENZYME STRUCTURE; GENE MUTATION; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN METABOLISM; PROTEIN PROCESSING; PROTEIN TARGETING; STRUCTURE ACTIVITY RELATION;

AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; DRUG DESIGN; HUMANS; PROTEASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33750152299     PISSN: 16602854     EISSN: 16602862     Source Type: Journal    
DOI: 10.1159/000095269     Document Type: Conference Paper

References (33)

1. WHO: The World Health Report 2001 Mental Health: New Understanding, New Hope. Geneva, WHO, 2001.
2. Schmidt B: Aspartic proteases involved in Alzheimer's disease. Chembiochem 2003;4:366-378.
3. Schmidt B, Baumann S, Braun HA, Larbig G: Inhibitors and modulators of β- and γ-secretase. Curr Top Med Chem 2006;6:377-392.
4. Schmidt B, Braun HA, Narlawar R: Drug development and PET-diagnostics for Alzheimer's disease. Curr Med Chem 2005;12:1677-1695.
5. Roggo S: Inhibition of BACE, a promising approach to Alzheimer's disease therapy. Curr Top Med Chem 2002;2:359-370.
6. John V, Beck JP, Bienkowski MJ, Sinha S, Heinrikson RL: Human β-secretase (BACE) and BACE inhibitors. J Med Chem 2003;46:4625-4630.
7. Ghosh AK, Hong L, Tang J: β-Secretase as a therapeutic target for inhibitor drugs. Curr Med Chem 2002;9:1135-1144.
8. Hong L, Turner RT III, Koelsch G, Shin D, Ghosh AK, Tang J: Crystal structure of memapsin 2 (β-secretase) in complex with an inhibitor OM00-3. Biochemistry 2002;41:10963-10967.
9. Maillaird M, Hom C, Gailunas A: Preparation of substituted amines to treat Alzheimer's disease. WO 200202512, 2002.
10. Braun HA, Meusinger R, Schmidt B: 2-Iodo-ethanols from aldehydes, diiodomethane and isopropylmagnesium chloride. Tet Lett 2005;46:2551-2554.
11. Miyamoto M, Matsui J, Fukumoto H, Tarui N: Preparation of 2-[2-amino- or 2-(N-heterocyclyl)ethyl]-6-(4-biphenylyl-methoxy)-tetralin derivatives as β-secretase inhibitors. WO 0187293, 2001.
12. Ramakrishna NVS, Kumar EKSV, Kulkarni AS: Screening of natural products for new leads as inhibitors of b-amyloid production: Latifolin from Dalbergia sissoo. Indian J Chem 2001;40B:539-540.
13. Barrow JC, Coburn CA, Nantermet PG: Preparation of phenylamides and pyridylamides as 1-secretase inhibitors. WO2005065195, 2005.
14. Stachel SJ, Coburn CA, Steele TG, et al: Conformationally biased P3 amide replacements of beta-secretase inhibitors. Bioorg Med Chem Lett 2006;16:641-644.
15. Yehia NA, Antuch W, Beck B, et al: Novel nonpeptidic inhibitors of HIV-1 protease obtained via a new multicomponent chemistry strategy. Bioorg Med Chem Lett 2004;14:3121-3125.
16. Thaisrivongs S, Strohbach JW: Structure-based discovery of tipranavir disodium (PNU-140690E): a potent, orally bioavailable, nonpeptidic HIV protease inhibitor. Biopolymers 1999;51:51-58.
17. Godel T, Hilpert H, Humm R: Preparation of tetronic and tetramic acids as beta-secretase inhibitors. WO 2005119329, 2005.
18. Larbig G, Schmidt B: Synthesis of tetramic and tetronic acid as beta-secretase inhibitors. J Comb Chem 2006;8:480-490.
19. Shearman MS, Beher D, Clarke EE, et al: L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity. Biochemistry 2000;39:8698-8704.
20. Lichtenthaler SF, Wang R, Grimm H, Uljon SU, Masters CL, Beyreuther K: Mechanism of the cleavage specificity of Alzheimer's diseases γ-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. PNAS 1999;96:3053-3058.
21. Dovey HF, John V, Anderson JP, et al: Functional γ-secretase inhibitors reduce b-amyloid peptide levels in brain. J Neurochem 2001;76:173-181.
22. Geling A, Steiner H, Willem M, Bally-Cuif L, Haass C: A γ-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO Rep 2002;3:688-694.
23. Larbig G, Zall A, Schmidt B: Inhibitors designed for presenilin 1 utilizing by means of aspartic acid activation. Helv Chim Acta 2004;87:2334-2340.
24. Netzer WJ, Dou F, Cai D, et al: Gleevec inhibits beta-amyloid production but not Notch cleavage. PNAS 2003;100:12444-12449.
25. Weggen S, Eriksen JL, Das P, et al: A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity. Nature 2001;414:212-216.
26. Lanz TA, Fici GJ, Merchant KM: Lack of specific amyloid-beta(1-42) suppression by nonsteroidal anti-inflammatory drugs in young, plaque-free Tg2576 mice and in guinea pig neuronal cultures. J Pharmacol Exp Ther 2005;312:399-406.
27. Beher D, Clarke EE, Wrigley JD, et al: Selected non-steroidal anti-inflammatory drugs and their derivatives target gamma-secretase at a novel site. Evidence for an allosteric mechanism. J Biol Chem 2004;279:43419-43426.
28. Kornilova AY, Das C, Wolfe MS: Differential effects of inhibitors on the γ-secretase complex. J Biol Chem 2003;278:16470-16473.
29. Cheng S, Comer DD, Mao L, Balow GP, Pleynet D: Aryl compounds and uses in modulating amyloid β. WO 2004110350, 2004.
30. Beher D, Bettati M, Checksfield GD: Preparation of tetrahydrocarbazole-1- alkanoic acids for the treatment of Alzheimer's disease and related conditions. WO 2005013985, 2005.
31. Schmidt B, Ehlert DK, Braun HA: E-1,2-dichlorovinyl ethers as irreversible protease inhibitors. Tet Lett 2004;45:1751-1753.
32. Braun HA, Umbreen S, Groll M, et al: Tripeptide mimetics inhibit the 20 S proteasome by covalent bonding to the active threonines. J Biol Chem 2005;280:28394-28401.
33. Schmidt B, Siegler A: Aspartic proteases involved in Alzheimer's disease; in Schmuck C, Wennemers H (eds): Highlights in Bioorganic Chemistry. Weinheim, Wiley-VCH, 2004, pp 262-276.