Rational Design and Synthesis of Potent Dibenzazepine Motifs as β-Secretase Inhibitors
Journal of Medicinal Chemistry2009Vol. 52(20), pp. 6484–6488
Citations Over TimeTop 15% of 2009 papers
Taleb H. Al‐Tel, Raed A. Al‐Qawasmeh, Marco F. Schmidt, Amal Al‐Aboudi, Shashidhar N. Rao, Salim S. Sabri, Wolfgang Voelter
Abstract
We have identified small-molecule dibenzazepine inhibitors of beta-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 (K(I) = 211 nM).
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