Synthesis of tetramic and tetronic acids as beta-secretase inhibitors

摘要

The aspartic protease beta-secretase (BACE-1) is an attractive target for the therapy of Alzheimer's disease. The known inhibitors share a high analogy to the substrate peptide and, thus, display undesired pharmacological properties. Compact nonpeptidic lead structures are scarce. Here, we report the activities of tetronic and tetramic acids on BACE-1 inhibition. The compounds feature a low molecular weight and compact scaffold, which is accessible by solid-phase-supported diverse synthesis.