title: 1,3-Oxazines as BACE1 and/or BACE2 inhibitors: a patent evaluation (WO2012156284).
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.
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, K-15-A211, USA. eric.gilbert@merck.com.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Gilbert
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D010078:Oxazines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010330:Patents as Topic
chemical_list: D007004:Hypoglycemic Agents; D010078:Oxazines; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human