Sandbox Reserved 817: Difference between revisions

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 One of the discovered compound, 1-(2-(1H-indol-1-yl)ethyl)guanidine showed weak inhibition activity towards BACE1 (about 42% inhibition ratio at the ligand concentration of 100 μM in the fluorescence resonance energy transfer (FRET) assay system). These compound occupied the S1 pocket and the guanidine moiety formed key binding interactions with the two catalytic aspartic acids, <scene name='56/568015/32/1'>Asp32</scene> and <scene name='56/568015/Asp228/1'>Asp228</scene> (Figure 2).
-As shown in some known BACE1 inhibitors in which the guanidine group is usually acylated, a compound was designed by introducing a carbonyl group into the α-position of the guanidine moiety.
+Some known BACE1 inhibitors have an an acetylated guanidine group. Some compounds were designed by introducing a carbonyl group into the α-position of the guanidine moiety to increase the inhibitor efficiency.
 To further improve the activity of this series of indole acylguanidines toward BACE1, the predicted conformation of inhibitors was scrutinized in the binding site of BACE1. There is a large hydrophobic sub-site at the top of the guanidine moiety. A benzyl group extending from the terminus of the guanidine moiety could fill this sub-pocket and thereby potentially increase the binding affinity. Analogs were synthesized based on indole and ethyl bromoacetate.