| Structural highlights
4pzx is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Related: | 4pzw |
| Activity: | Memapsin 2, with EC number 3.4.23.46 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
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=110nM) demonstrated a reduction in CSF Abeta in wild type rats after a single dose.
Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors.,Volgraf M, Chan L, Huestis MP, Purkey HE, Burkard M, Geck Do M, Harris J, Hunt KW, Liu X, Lyssikatos JP, Rana S, Thomas AA, Vigers GP, Siu M Bioorg Med Chem Lett. 2014 Jun 1;24(11):2477-80. doi: 10.1016/j.bmcl.2014.04.012., Epub 2014 Apr 13. PMID:24780121[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Volgraf M, Chan L, Huestis MP, Purkey HE, Burkard M, Geck Do M, Harris J, Hunt KW, Liu X, Lyssikatos JP, Rana S, Thomas AA, Vigers GP, Siu M. Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors. Bioorg Med Chem Lett. 2014 Jun 1;24(11):2477-80. doi: 10.1016/j.bmcl.2014.04.012., Epub 2014 Apr 13. PMID:24780121 doi:http://dx.doi.org/10.1016/j.bmcl.2014.04.012
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