P2’-truncated BACE-1 inhibitors with a novel hydroxethylene-like core
2010 (English)In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 45, no 2, 542-554 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Elsevier Masson SAS , 2010. Vol. 45, no 2, 542-554 p.
Research subject Organic Chemistry
IdentifiersURN: urn:nbn:se:su:diva-29559DOI: 10.1016/j.ejmech.2009.10.041ISI: 000274773300016OAI: oai:DiVA.org:su-29559DiVA: diva2:234155