4exg | pdb_00004exg
Design and synthesis of potent hydroxyethylamine (hea) bace-1 inhibitors
Structural highlights
FunctionBACE1_HUMAN Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.[1] [2] Publication Abstract from PubMedA 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). 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.,Sund C, Belda O, Borkakoti N, Lindberg J, Derbyshire D, Vrang L, Hamelink E, Ahgren C, Woestenenk E, Wikstrom K, Eneroth A, Lindstrom E, Kalayanov G Bioorg Med Chem Lett. 2012 Nov 1;22(21):6721-7. doi: 10.1016/j.bmcl.2012.08.097. , Epub 2012 Sep 5. PMID:23010268[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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