4-Oxo-1,4-dihydro-quinoline-3-carboxamides as BACE-1 inhibitors: Synthesis, biological evaluation and docking studies

• Novel 4-oxo-1,4-dihydro-quinoline-3-carboxamide motif with BACE-1 were reported.
• A series of 6-substituted derivatives as novel BACE-1 inhibitors were synthesized.
• Compounds 14d and 14e were good drug-like profiles for further modification.

In this work, we report a series of new 4-oxo-1,4-dihydro-quinoline-3-carboxamide derivatives as β-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. The studies revealed that the most potent analog 14e (IC50 = 1.89 μM) with low cellular cytotoxicity and high predicted blood brain barrier permeability, could serve as a good structure for further modification.

A series of 4-oxo-1,4-dihydro-quinoline-3-carboxamids were designed from 1 as BACE-1 inhibitors, among which 14e exhibited better drugabilities including improved inhibitory potency, low cytotoxicity and possibility to penetrate BBB.Figure optionsDownload as PowerPoint slide