Design, Synthesis, and Crystal Structure of Hydroxyethyl Secondary Amine-Based Peptidomimetic Inhibitors of Human β-Secretase

Michel Maillard(Pfizer (United States)), Roy K. Hom(Pfizer (United States)), Timothy E. Benson(Pfizer (United States)), Joseph B. Moon(Pfizer (United States)), Shumeye Mamo(Pfizer (United States)), Michael J. Bienkowski(Pfizer (United States)), Alfredo G. Tomasselli(Pfizer (United States)), Danielle D. Woods(Pfizer (United States)), D. Bryan Prince(Pfizer (United States)), Donna J. Paddock(Pfizer (United States)), Thomas L. Emmons(Pfizer (United States)), John A. Tucker(Pfizer (United States)), Michael S. Dappen(Pfizer (United States)), Louis Brogley(Pfizer (United States)), Eugene D. Thorsett(Pfizer (United States)), Nancy Jewett(Pfizer (United States)), Sukanto Sinha(Pfizer (United States)), Varghese John(Pfizer (United States))
Journal of Medicinal Chemistry
January 10, 2007
Cited by 111Open Access
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Abstract

The design and synthesis of a novel series of potent and cell permeable peptidomimetic inhibitors of the human beta-secretase (BACE) are described. These inhibitors feature a hydroxyethyl secondary amine isostere and a novel aromatic ring replacement for the C-terminus. The crystal structure of BACE in complex with this hydroxyethyl secondary amine isostere inhibitor is also presented.


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