4J1C: CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH 5-Cyano-pyridine-2-carboxylic acid [3-((S)-2-amino-5,5-difluoro-4-fluoromethyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-amide

Citation:
Abstract
An extensive fluorine scan of 1,3-oxazines revealed the power of fluorine(s) to lower the pKa and thereby dramatically change the pharmacological profile of this class of BACE1 inhibitors. The CF3 substituted oxazine 89, a potent and highly brain penetrant BACE1 inhibitor, was able to reduce significantly CSF Abeta40 and 42 in rats at oral doses as low as 1 mg/kg. The effect was long lasting, showing a significant reduction of Abeta40 and 42 even after 24 h. In contrast to 89, compound 1b lacking the CF3 group was virtually inactive in vivo.
PDB ID: 4J1CDownload
MMDB ID: 109668
PDB Deposition Date: 2013/2/1
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.01  Å
Source Organism:
Similar Structures:
Biological Unit for 4J1C: monomeric; determined by author and by software (PISA)
Molecular Components in 4J1C
Label Count Molecule
Protein (1 molecule)
1
Beta-secretase 1(Gene symbol: BACE1)
Molecule annotation
Chemicals (4 molecules)
1
2
2
1
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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