Design and synthesis of potent and selective BACE-1 inhibitors

• Several highly potent BACE-1 protease inhibitors have been developed from an inhibitor series containing a novel hydroxyethylene (HE) core structure displaying aryloxymethyl or benzyloxymethyl P1 side chains and a methoxy P1’ side chain. The target molecules were readily synthesized from chiral carbohydrate starting materials, furnishing the inhibitor compounds in good overall yields. The inhibitors show both high BACE-1 potency and good selectivity against cathepsin D, where the most potent inhibitor furnish a BACE-1 IC50 value of 0.32 nM and displays > 3000 fold selectivity over cathepsin D.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

Keyword

Pharmaceutical chemistry

Läkemedelskemi

organisk kemi

Organic Chemistry

MEDICINE

Publication and Content Type

ref (subject category)

art (subject category)