1216934-97-2Relevant academic research and scientific papers
ASPARTYL PROTEASE INHIBITORS
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Page/Page column 120, (2010/04/28)
A compound of formula (I): N-oxides, addition salts, quaternary amines metal complexes stereochemically isomeric forms and metabolites thereof, wherein A is CR1 or N; D is H, C1-C6alkyl, C2-C6alkenyl,
P2′-truncated BACE-1 inhibitors with a novel hydroxethylene-like core
Meredith, Jenny Adrian,Bj?rklund, Catarina,Adolfsson, Hans,Jansson, Katarina,Hallberg, Anders,Rosenquist, ?sa,Samuelsson, Bertil
experimental part, p. 542 - 554 (2010/04/06)
Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2′ amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-1 IC50 value of 140 nM. The synthesis of these BACE-1 inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields.
