1, 3-Oxazines as BACE1 and/or BACE2 inhibitors: a patent evaluation (WO2012156284). (August 2013)

• Record Type: Journal Article
• Authors: Gilbert, Eric J
• Is Part Of: Expert opinion on therapeutic patents. Volume 23:Number 8(2013:Aug.)
• Page Start: 1069
• Page End: 1073
• Publication Date: 2013-08
• Subjects: Alzheimer's disease -- BACE1 -- BACE2 -- type 2 diabetes; Drugs -- Patents -- Periodicals; 615.10272
• DOI: 10.1517/13543776.2013.818134
• Languages: English
• ISSNs: 1354-3776

Abstract

Abstract : This patent review covers the contents of Hoffman-La Roche and Siena Biotech's patent application WO2012156284 titled '1, 3-Oxazines as BACE1 and/or BACE2 Inhibitors.' Beta-site amyloid precursor protein-converting enzyme (BACE1) and BACE2 activities are reported to support the claimed compounds' use as therapeutics for Alzheimer's disease and type II diabetes, respectively. A common core motif of the claimed compounds is the six-membered 1, 3-oxazine system. To gain access to the S3 and S3 subpocket of the BACE1 active site, various linkers are described including nitrogen- and oxygen-based, aryl, and amide-based linkers. Of the 65 compounds claimed, 6 had IC50s less than 100 nM in the BACE1 cell assay. Cellular BACE2 inhibition data are reported for 20 compounds with 2 under 100 nM.