2-Substituted-thio-N-(4-substituted-thiazo1/1H-imidazol-2-yl) acetamides as BACE1 inhibitors: Synthesis, biological evaluation and docking studies

摘要

In this work, a series of 2-substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamide derivatives were developed as beta-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. In addition, the selected compounds were tested with affinity (K-D) towards BACE-1, blood brain barrier (BBB) permeability and cytotoxicity. The studies revealed that the most potent analog 41 (IC50 = 4.6 mu M) with high predicted BBB permeability and low cellular cytotoxicity, could serve as a good lead structure for further optimization. (C) 2017 Elsevier Masson SAS. All rights reserved.