Bioorganic & Medicinal Chemistry Letters 2006-02-01

Conformationally biased P3 amide replacements of beta-secretase inhibitors.

Shawn J Stachel, Craig A Coburn, Thomas G Steele, Min-Chi Crouthamel, Beth L Pietrak, Ming-Tain Lai, M Katharine Holloway, Sanjeev K Munshi, Samuel L Graham, Joseph P Vacca

Index: Bioorg. Med. Chem. Lett. 16(3) , 641-4, (2006)

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Abstract

We have synthesized and evaluated a series of conformationally biased P3 amide replacements based on an isophthalamide lead structure. The studies resulted in the identification of the beta-secretase inhibitor 7m which has an in vitro IC(50)=35 nM. The synthesis and biological activities of these compounds are described.