�-Secretase (BACE1) inhibition remains a key focus of Alzheimer's disease (AD) research due to its potential slow or halt disease progression without mechanism-based toxicity. Through rational, structure-based design, we identified an iminopyrimidinone binding motif that produces BACE1 inhibitors with good potency and moderate cell shifts. SAR for a variety of P1-P3 biaryl analogs in this series, as well as selected in vivo activity and chemistry to generate these structures will be presented.

Novel iminopyrimidinone β-Secretase inhibitors: Part 1. P1-P3 SAR

239th National Meeting (2010)

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