4EXG

Design and synthesis of potent hydroxyethylamine (hea) bace-1 inhibitors

Summary for 4EXG

• Entry DOI: 10.2210/pdb4exg/pdb
• Related: 4EWO
• Descriptor: Beta-secretase 1, N-[(2S,3R)-4-{[(4S)-6-(2,2-dimethylpropyl)-2,2-dimethyl-3,4-dihydro-2H-thieno[2,3-b]pyran-4-yl]amino}-3-hydroxy-1-phenylbutan-2-yl]acetamide (3 entities in total)
• Functional Keywords: bace, beta-secretase, statine, inhibitor, aspartyl protease, glycoprotein, membrane, protease, transmembrane, zymogen, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 1
• Total formula weight: 43480.16

Authors

Borkakoti, N.,Lindberg, J.,Derbyshire, D. (deposition date: 2012-04-30, release date: 2012-10-31, Last modification date: 2024-11-20)

Primary citation

Sund, C.,Belda, O.,Borkakoti, N.,Lindberg, J.,Derbyshire, D.,Vrang, L.,Hamelink, E.,Hgren, C.,Woestenenk, E.,Wikstrom, K.,Eneroth, A.,Lindstrom, E.,Kalayanov, G.
Design and synthesis of potent hydroxyethylamine (HEA) BACE-1 inhibitors carrying prime side 4,5,6,7-tetrahydrobenzazole and 4,5,6,7-tetrahydropyridinoazole templates.
Bioorg.Med.Chem.Lett., 22:6721-6727, 2012

PubMed Abstract: A set of low molecular weight compounds containing a hydroxyethylamine (HEA) core structure with different prime side alkyl substituted 4,5,6,7-tetrahydrobenzazoles and one 4,5,6,7-tetrahydropyridinoazole was synthesized. Striking differences were observed on potencies in the BACE-1 enzymatic and cellular assays depending on the nature of the heteroatoms in the bicyclic ring, from the low active compound 4 to inhibitor 6, displaying BACE-1 IC(50) values of 44 nM (enzyme assay) and 65 nM (cell-based assay).

PubMed: 23010268
DOI: 10.1016/j.bmcl.2012.08.097

Experimental method

X-RAY DIFFRACTION (1.8 Å)