Synthesis of Cyclopropyl Peptidomimetics as BACE Inhibitors

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Akter, Mahmuda
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University Honors College, Middle Tennessee State University
Since the development of the amyloid hypothesis, correlating the production of amyloid plaques to the pathology of the Alzheimer’s disease, numerous research groups have worked on developing an inhibitor for the BACE1 protease which is considered to be primarily responsible for the cleavage of Amyloid-Precursor Protein leading to the formation of amyloid-beta plaques. Our laboratory has attempted to synthesize peptidomimetic inhibitors with a cyclopropyl core. While an effective route has been developed for a series of amides, there were difficulties in synthesizing a particular series of compounds with a reverse amide. Hence, we have used synthetic routes developed in this lab to design a new scheme in order to synthesize analogs of cyclopropyl peptidomimetic with the isophthalamide side chain and a reverse amide.
BACE, alzheimers, peptidomimeties, cyclopropyl, reverse amide, BACE inhisibors