1378683-82-9Relevant academic research and scientific papers
Discovery of amino-1,4-oxazines as potent BACE-1 inhibitors
Veenstra, Siem Jakob,Rueeger, Heinrich,Voegtle, Markus,Lueoend, Rainer,Holzer, Philipp,Hurth, Konstanze,Tintelnot-Blomley, Marina,Frederiksen, Mathias,Rondeau, Jean-Michel,Jacobson, Laura,Staufenbiel, Matthias,Neumann, Ulf,Machauer, Rainer
, p. 2195 - 2200 (2018)
New amino-1,4-oxazine derived BACE-1 inhibitors were explored and various synthetic routes developed. The binding mode of the inhibitors was elucidated by co-crystallization of 4 with BACE-1 and X-ray analysis. Subsequent optimization led to inhibitors with low double digit nanomolar activity in a biochemical and single digit nanomolar potency in a cellular assays. To assess the inhibitors for their permeation properties and potential to cross the blood-brain-barrier a MDR1-MDCK cell model was successfully applied. Compound 8a confirmed the in vitro results by dose-dependently reducing Aβ levels in mice in an acute treatment regimen.
Transaminases as suitable catalysts for the synthesis of enantiopure β,β-difluoroamines
García-Ramos, Marina,Lavandera, Iván
supporting information, p. 984 - 988 (2022/02/16)
Transaminases have shown the ability to catalyze the amination of a series of aliphatic and (hetero)aromatic α,α-difluorinated ketones with high stereoselectivity, thus providing the corresponding β,β-difluoroamines in high isolated yields (55–82%) and ex
Direct and Chemoselective Synthesis of Tertiary Difluoroketones via Weinreb Amide Homologation with a CHF2-Carbene Equivalent
Miele, Margherita,Citarella, Andrea,Micale, Nicola,Holzer, Wolfgang,Pace, Vittorio
supporting information, p. 8261 - 8265 (2019/10/16)
The homologation of Weinreb amides into difluoromethylketones with a formal nucleophilic CHF2 transfer agent is reported. Activating TMSCHF2 with potassium tert-amylate enables a convenient access to the difluorinated homologation re
2-Amino-6-(difluoromethyl)-5,5-difluoro-6-phenyl-3,4,5,6-tetrahydropyridines as BACE1 Inhibitors
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Paragraph 0106; 0107, (2016/06/01)
The present invention is directed to novel inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of Aβ d
DIHYDROOXAZINE OR OXAZEPINE DERIVATIVES HAVING BACE1 INHIBITORY ACTIVITY
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Paragraph 0167, (2014/05/24)
The present invention provides a compound which has an effect of inhibiting amyloid beta production, especially an effect of inhibiting BACE1, and which is useful as a therapeutic or prophylactic agent for diseases induced by production, secretion and/or
FLUOROMETHYL-5,6-DIHYDRO-4H-[1,3]OXAZINES
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Page/Page column 52, (2013/08/15)
The present invention provides a compound of formula (I) having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease
