Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives

We describe synthesis and evaluation of a series of cyclic urea derivatives with hydroxylethylamine isostere. Modification of P3, P1, and P2′ and combination of SAR display a >100-fold increase in potency with good cellular activity (IC50 = 0.15 μM) relative to the previously reported compound 3.

Compound 26 showed excellent inhibitory activity against BACE-1, good selectivity over Cathepsin D.Figure optionsDownload as PowerPoint slide