Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796): A γ-secretase inhibitor with Aβ lowering activity in a transgenic mouse model of Alzheimer's disease

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 14, 2007, Pages 4006-4011

  Prasad, C V C ^a   Zheng, Ming ^a   Vig, Shikha ^a   Bergstrom, Carl ^a   Smith, David W ^a   Gao, Qi ^a   Yeola, Suresh ^a   Polson, Craig T ^a   Corsa, Jason A ^a   Guss, Valerie L ^a   Loo, Alice ^a   Wang, Jian ^a   Sleczka, Bogdan G ^a   Dangler, Charles ^a   Robertson, Barbara J ^a   Hendrick, Joseph P ^a   Roberts, Susan B ^a   Barten, Donna M ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Sectretase inhibitors

Indexed keywords

2 [2 (3,5 DIFLUOROPHENYL) 2 HYDROXYACETAMIDO] N (3 METHYL 4 OXO 4,5 DIHYDRO 3H BENZO[D][1,2]DIAZEPIN 5 YL)PROPANAMIDE; AMYLOID BETA PROTEIN; BENZODIAZEPINE DERIVATIVE; BMS 433796; GAMMA SECRETASE INHIBITOR; NOTCH RECEPTOR; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG DESIGN; DRUG MEGADOSE; DRUG POTENCY; DRUG SYNTHESIS; MALE; MOUSE; NONHUMAN; PHARMACODYNAMICS; STRUCTURE ACTIVITY RELATION; TRANSGENIC MOUSE;

ALANINE; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; BENZODIAZEPINONES; ENZYME INHIBITORS; MICE; MICE, TRANSGENIC; MODELS, MOLECULAR;

MUS; MUS MUSCULUS;

EID: 34250365682     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.04.082     Document Type: Article

References (31)

1. Neurobiol. Aging 1997, 18, S1.
2. Tanzi R.E., and Bertram L. Cell 120 (2005) 545
3. Klein W.L. Alzheimer's & Dement. 2 (2006) 43
4. Selkoe D.J. Physiol. Rev. 81 (2001) 741
5. Schmidt B., Baumann S., Braun H.A., and Larbig G. Curr. Top. Med. Chem. 6 (2006) 377
6. Churcher I., and Beher D. Curr. Pharm. Des. 11 (2005) 3363
7. Brunkan A.L., and Goate A.M. J. Neurochem. 93 (2005) 769
8. Wolfe M.S., Citron M., Diehl T.S., Xia W., Donkor I.O., and Selkoe D.J. J. Med. Chem. 41 (1998) 6
9. Nadin A., Owens A.P., Castro J.L., Harrison T., and Shearman M.S. Bioorg. Med. Chem. Lett. 13 (2003) 37
10. Siemers E., Skinner M., Dean R.A., Gonzales C., Satterwhite J., Farlow M., Ness D., and May P.C. Clin. Neuropharmacol. 28 (2005) 126
11. Dovey H.F., John V., Anderson J.P., Chen L.Z., de Saint Andrieu P., Fang L.Y., Freedman S.B., Folmer B., Goldbach E., Holsztynska E.J., Hu K.L., Johnson-Wood K.L., Kennedy S.L., Kholodenko D., Knops J.E., Latimer L.H., Lee M., Liao Z., Lieberburg I.M., Motter R.N., Mutter L.C., Nietz J., Quinn K.P., Sacchi K.L., Seubert P.A., Shopp G.M., Thorsett E.D., Tung J.S., Wu J., Yang S., Yin C.T., Schenk D.B., May P.C., Altstiel L.D., Bender M.H., Boggs L.N., Britton T.C., Clemens J.C., Czilli D.L., Dieckman-McGinty D.K., Droste J.J., Fuson K.S., Gitter B.D., Hyslop P.A., Johnstone E.M., Li W.Y., Little S.P., Mabry T.E., Miller F.D., and Audia J.E. J. Neurochem. 76 (2001) 173
12. Smith, D. W.; Munoz, B.; Srinivasan, K.; Bergstrom, C., P; Chaturvedula, P. V.; Deshpande, M. S.; Keavy, D. J.; Lau, W. Yu; Parker, M. F.; Sloan, C. P.; Wallace, O. B.; Wang, H. Hui, US Patent 6,967,196, 2005; Chem. Abstr. 2000, 133, 207678.
13. Rishton G.M., Retz D.M., Tempest P.A., Novotny J., Kahn S., Treanor J.J., Lile J.D., and Citron M. J. Med. Chem. 43 (2000) 2297
14. Thompson L.A., Liauw A.Y., Ramanjulu M.M., Kasireddy-Polam P., Mercer S.E., Maduskuie T.P., Glicksman M., Roach A.H., Meredith J.E., Liu R.Q., Combs A.P., Higaki J.N., Cordell B., Seiffert D., Zaczek R.C., Robertson D.W., and Olson R.E. Bioorg. Med. Chem. Lett. 16 (2006) 2357
15. Churcher I., Beher D., Best J.D., Castro J.L., Clarke E.E., Gentry A., Harrison T., Hitzel L., Kay E., Kerrad S., Lewis H.D., Morentin-Gutierrez P., Mortishire-Smith R., Oakley P.J., Reilly M., Shaw D.E., Shearman M.S., Teall M.R., Williams S., and Wrigley J.D. Bioorg. Med. Chem. Lett. 16 (2006) 280
16. Jelley R.A., Elliott J., Gibson K.R., Harrison T., Beher D., Clarke E.E., Lewis H.D., Shearman M., and Wrigley J.D.J. Bioorg. Med. Chem. Lett. 16 (2006) 3839
17. Shaw D., Best J., Dinnell K., Nadin A., Shearman M., Pattison C., Peachey J., Reilly M., Williams B., Wrigley J., and Harrison T. Bioorg. Med. Chem. Lett. 16 (2006) 3073
18. Teall M., Oakley P., Harrison T., Shaw D., Kay E., Elliott J., Gerhard U., Castro J.L., Shearman M., Ball R.G., and Tsou N.N. Bioorg. Med. Chem. Lett. 15 (2005) 2685
19. Lewis S.J., Smith A.L., Neduvelil J.G., Stevenson G.I., Lindon M.J., Jones A.B., Shearman M.S., Beher D., Clarke E., Best J.D., Peachey J.E., Harrison T., and Castro J.L. Bioorg. Med. Chem. Lett. 15 (2005) 373
20. Sparey T., Beher D., Best J., Biba M., Castro J.L., Clarke E., Hannam J., Harrison T., Lewis H., Madin A., Shearman M., Sohal B., Tsou N., Welch C., and Wrigley J. Bioorg. Med. Chem. Lett. 15 (2005) 4212
21. Neitzel, M.; Dappen, M. S.; Marugg, J.; WO 04248 2005; Chem. Abstr. 2005, 142 463620.
22. Galley, G.; Goodnow, R. A.; Peters, J.-U. US Patent 7,060,698, 2006; Chem. Abstr. 2004, 142, 6564.
23. Rosen L., Stone J., Plump A., Yuan J., Harrison T., Flynn M., Dallob A., Matthews C., Stevenson D., Schmidt D., Palmieri T., Leibowitz M., Jhee S., Ereshefsky L., Salomon R., Winchell G., Shearman M., Murphy M., and Gottesdiener K. Alzheimer's & Dement.: J. Alzheimer's Assoc. 2 (2006) S79
24. Prasad C.V.C., Vig S., Smith D.W., Gao Q., Polson C.T., Corsa J.A., Guss V.L., Loo A., Barten D.M., Zheng M., Felsenstein K.M., and Roberts S.B. Bioorg. Med. Chem. Lett. 14 (2004) 3535
25. Prasad C.V.C., Wallace O.B., Noonan J.W., Sloan C.P., Lau W., Vig S., Parker M.F., Smith D.W., Hansel S.B., Polson C.T., Barten D.M., Felsenstein K.M., and Roberts S.B. Bioorg. Med. Chem. Lett. 14 (2004) 1917
26. Barten D.M., Guss V.L., Corsa J.A., Loo A., Hansel S.B., Zheng M., Munoz B., Srinivasan K., Wang B., Robertson B.J., Polson C.T., Wang J., Roberts S.B., Hendrick J.P., Anderson J.J., Loy J.K., Denton R., Verdoorn T.A., Smith D.W., and Felsenstein K.M. J. Pharmacol. Exp. Ther. 312 (2005) 635
27. Evans D.A., Brittan T.C., Ellman J.A., and Dorow R.L. J. Am. Chem. Soc. 112 (1990) 4011
28. Lanz T.A., Karmilowicz M.J., Wood K.M., Pozdnyakov N., Du P., Piotrowski M.A., Brown T.M., Nolan C.E., Richter K.E., Finley J.E., Fei Q., Ebbinghaus C.F., Chen Y.L., Spracklin D.K., Tate B., Geoghegan K.F., Lau L.F., Auperin D.D., and Schachter J.B. J. Pharmacol. Exp. Ther. 319 (2006) 924
29. Full crystallographic data have been deposited with the Cambridge Crystallographic Data Center (CCDC reference number 639765). Copies of the data can be obtained free of charge via the internet at http://www.ccdc.cam.ac.uk.
30. Lewis J. Semin. Cell Dev. Biol. 9 (1998) 583
31. Barten D.M., Meredith Jr. J.E., Zaczek R., Houston J.G., and Albright C.F. Drugs RD 7 (2006) 87