4PZX: Synthesis, Characterization And Pk/pd Studies Of A Series Of Spirocyclic Pyranochromene Bace1 Inhibitors

Citation:
Abstract
The development of 1,3,4,4a,5,10a-hexahydropyrano[3,4-b]chromene analogs as BACE1 inhibitors is described. Introduction of the spirocyclic pyranochromene scaffold yielded several advantages over previous generation cores, including increased potency, reduced efflux, and reduced CYP2D6 inhibition. Compound 13 (BACE1 IC50=110 nM) demonstrated a reduction in CSF Abeta in wild type rats after a single dose.
PDB ID: 4PZXDownload
MMDB ID: 119492
PDB Deposition Date: 2014/3/31
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4PZX: monomeric; determined by author and by software (PISA)
Molecular Components in 4PZX
Label Count Molecule
Protein (1 molecule)
1
Beta-secretase 1(Gene symbol: BACE1)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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