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B. Hu et al. / Bioorg. Med. Chem. Lett. 14 (2004) 3457–3460
5. For molecular modeling studies on BACE 1, see: (a)
References and notes
Tounge, B. A.; Reynolds, C. H. J. Med. Chem. 2003, 46,
2074; (b) Fan, K. Y.; Hu, B.; Cole, D.; Bridges, K.;
Chopra, R.; Manas, E. S.; Katz, A.; Alvarez, J. C.;
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Abstracts of Papers, 226th ACS National Meeting, New
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134.
1. For recent reviews on BACE 1, see: (a) Varghese, J.; Beck,
J. P.; Bienkowski, M. J.; Sinha, S.; Heinrikson, R. L. J.
Med. Chem. 2003, 46, 4625; (b) Vassar, R. Adv. Drug
Deliv. Rev. 2002, 54, 1589; (c) Vassar, R. J. Mol. Neurosci.
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Chem. 2002, 9, 1135; (e) Roggo, S. Curr. Top. Med. Chem.
2002, 2, 359.
2. For recent papers on statine-containing BACE 1 inhibitors
see: (a) Tung, J. S.; Davis, D. L.; Anderson, J. P.; Walker,
D. E.; Mamo, S.; Jewett, N.; Hom, R. K.; Sinha, S.;
Thorsett, E. D.; John, V. J. Med. Chem. 2002, 45, 259; (b)
Hu, J.; Cwi, C. L.; Smiley, D. L.; Timm, D.; Erickson, J.
A.; McGee, J. E.; Yang, H.; Mendel, D.; May, C. P.;
Shapiro, M.; McCarthy, J. R. Bioorg. Med. Chem. Lett.
2003, 13, 4335; (c) Hom, R. K.; Fang, L. Y.; Mamo, S.;
Tung, J. S.; Guinn, A. C.; Walker, D. E.; Davis, D. L.;
Gailunas, A. F.; Thorsett, E. D.; Sinha, S.; Knops, J. E.;
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6. For a preliminary account of SARs on bis-statine deriv-
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P.; Ellingboe, J.; Jin, G.; Cowling, R.; Bard, J. Abstracts,
58th Northwest Regional Meeting of the American
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12–14, 2003, 171.
7. All final compounds and novel intermediates were char-
acterized by 1H NMR, mass spectrometry, and high-
resolution mass spectrometry or CHN analysis.
8. BACE 1 inhibition was measured using recombinant
enzyme produced from mammalian expression as de-
scribed similarly in Ref. 2a. Fluorogenic substrate Abz-
SEVNL-DAEFR-DPa was used with 10 nM human
BACE 1 in 0.05 M Na-acetate þ 0.05% CHAPS and 25%
PBS, pH 4.5 at room temperature. The excitation wave-
length was 354 nm, and the emission wavelength was
280 nm. Details of this assay will be described shortly.
9. Mcmartin, C.; Bohacek, R. S. J. Comp.-Aided Mol. Des.
1997, 11, 333.
3. John, V.; Tung, J.; Fang, L.; Mamo, S. S. WO 0077030,
2000; Chem. Abstr. 2000, 134, 56968.
4. Bridges, K.; Chopra, R.; Lin, L.; Svenson, K.; Tam, A.;
Jin, G.; Cowling, R.; Lovering, L.; Akopian, L. N.; Bard,
J.; Elizabeth, D.; Bethany, A.; Edward, R. L.; Tod, H. M.;
Richard, S. Z.; William, S. S.; Mark, L. S.; Ronald, W. K.,
unpublished results.
10. Halgren, T. A. J. Comp. Chem. 1996, 17, 616, and the
references cited therein.
11. Drug Discovery Software SYBYL 6.7 developed by Tripos,
St. Louis, USA.