We have identified small-molecule dibenzazepine inhibitors of β-secretase (BACE1). These BACE1 inhibitors possess two key salient features. The first is a seven-membered heterocyclic ring fused to two aromatic rings representing the P3−P2 residues. The second is an amide and/or amide bioisostere representing the P1′ residue. Rational optimization led to the identification of potent analogues, such as 10 (KI = 211 nM).