Design and Synthesis of Potent and Selective BACE-1 Inhibitors
Catarina Björklund, Stefan Oscarson, Kurt Benkestock, Neera Borkakoti, Katarina Jansson, Jimmy Lindberg, Lotta Vrang, Anders Hallberg, Åsa Rosenquist, Bertil Samuelsson · Journal of Medicinal Chemistry · 2010
Highly potent BACE-1 protease inhibitors have been developed from an inhibitors containing a hydroxyethylene (HE) core displaying aryloxymethyl or benzyloxymethyl P1 side chain and a methoxy P1' side chain. The target molecules were synthesized in good overall yields from chiral carbohydrate starting materials. The inhibitors show high BACE-1 potency and good selectivity against cathepsin D, where the most potent inhibitor furnishes BACE-1 K(i) 1000-fold selectivity over cathepsin D.