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. 2000 Apr 12;122(14):3522-3523.
doi: 10.1021/ja000300g. Epub 2000 Mar 23.

Design of Potent Inhibitors for Human Brain Memapsin 2 (β-Secretase)

Arun K Ghosh  1 , Dongwoo Shin  1 , Debbie Downs  2 , Gerald Koelsch  2 , Xinli Lin  2 , Jacques Ermolieff  2 , Jordan Tang  2   3
Affiliations

Design of Potent Inhibitors for Human Brain Memapsin 2 (β-Secretase)

Arun K Ghosh et al. J Am Chem Soc. .
No abstract available

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Figures

Figure 1.
Figure 1.
Structures of OM99–1 (Val-Asn-Leu*Ala-Ala-Glu-Phe) and OM99–2 (Glu-Val-Asn-Leu*Ala-Ala-Glu-Phe) inhibitors. The asterisk in the sequence designates the hydroxyethylene transition-state isostere.
Figure 2.
Figure 2.
Inhibition of memapsin 2 activity toward fluorogenic substrate10. Ki values are described in the text.
Scheme 1
Scheme 1
a Reagents and conditions: (a) LiAlH4, Et2O, −40 °C, 30 min (86%);(b) LDA, HC≡C−CO2Et, THF, −78 °C, 30 min, then 4, −78 °C, 1 h (42%); (c) H2, Pd−BaSO4, EtOAc; (d) AcOH, PhMe, reflux, 6 h (74%);(e) LiHMDS, MeI, THF, −78 °C, 20 min (76%); (f) aqueous LiOH, THF-H2O, 23 °C, 10 h; (g) TBDMSCl, imidazole, DMF, 24 h (90%);(h) CF3CO2H, CH2Cl2, 0 °C, 1.5 h; (i) Fmoc-OSu, aqueous NaHCO3, dioxane, 23 °C, 8 h (61%).
See this image and copyright information in PMC

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