4PZW

Synthesis, Characterization and PK/PD Studies of a Series of Spirocyclic Pyranochromene BACE1 Inhibitors

4PZW の概要

• エントリーDOI: 10.2210/pdb4pzw/pdb
• 関連するPDBエントリー: 4PZX
• 分子名称: Beta-secretase 1, NICKEL (II) ION, (4R,4a'S,10a'S)-7'-(5-chloropyridin-3-yl)-3',4',4a',10a'-tetrahydro-1'H-spiro[1,3-oxazole-4,5'-pyrano[3,4-b]chromen]-2-amine, ... (4 entities in total)
• 機能のキーワード: aspartyl protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P56817
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45875.63

構造登録者

Vigers, G.P.A. (登録日: 2014-03-31, 公開日: 2014-05-14, 最終更新日: 2024-11-06)

主引用文献

Volgraf, M.,Chan, L.,Huestis, M.P.,Purkey, H.E.,Burkard, M.,Geck Do, M.,Harris, J.,Hunt, K.W.,Liu, X.,Lyssikatos, J.P.,Rana, S.,Thomas, A.A.,Vigers, G.P.,Siu, M.
Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors.
Bioorg.Med.Chem.Lett., 24:2477-2480, 2014

PubMed 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 Aβ in wild type rats after a single dose.

PubMed: 24780121
DOI: 10.1016/j.bmcl.2014.04.012

実験手法

X-RAY DIFFRACTION (1.8 Å)