P2 '-truncated BACE-1 inhibitors with a novel hydroxethylene-like core

Adrian Meredith, Jenny,1971-Stockholms universitet,Institutionen för organisk kemi,Bertil Samuelsson (author)

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-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields.

Björklund, Catarina,1981-Stockholms universitet,Institutionen för organisk kemi,Bertil Samuelsson(Swepub:su)cbj (author)
Adolfsson, HansStockholms universitet,Institutionen för organisk kemi,Hans Adolfsson(Swepub:su)hansa (author)
Jansson, Katarina (author)
Hallberg, AndersUppsala universitet,Institutionen för läkemedelskemi,Institutionen för läkemedelskemi, Uppsala universitet(Swepub:uu)andehall (author)
Rosenquist, Åsa (author)
Samuelsson, BertilStockholms universitet,Institutionen för organisk kemi(Swepub:su)bsamu (author)
Stockholms universitetInstitutionen för organisk kemi (creator_code:org_t)

In:European Journal of Medicinal Chemistry: Elsevier BV45:2, s. 542-5540223-52341768-3254

By the author/editor: Adrian Meredith, ...; Björklund, Catar ...; Adolfsson, Hans; Jansson, Katarin ...; Hallberg, Anders; Rosenquist, Åsa; show more...; Samuelsson, Bert ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medicinal Chemis ...

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