BACE-1 Activity of 4-Substituted-3,5-Dichlorobenzylamine Analogues

June 11, 2024

• Title:       

  BACE-1 Activity of 4-Substituted-3,5-Dichlorobenzylamine Analogues

• Image Source:

  Acyl guanidine inhibitors of β-secretase (bACE-1): Optimization of a micromolar hit to a nanomolar lead via iterative solid- and solution-phase library synthesis

• Mark:

  Table 4

• Associated context:

  As shown in Table 4, the 4-OH analogue 17a did not afford any improvement in BACE-1 activity, and the corresponding n-Pr ether 17b was inactive. However, the 4-NH₂ side chain provided a dramatic increase in activity with both the isoxazole  (17c, Ki = 120 nM) and isothiazole (17d, K_i = 40 nM) analogs. With an LE of 0.34 kcal/mol·heavy atom, 17d  provided a significant improvement in ligand efficiency.