Synthesis of tetramic and tetronic acids as beta-secretase inhibitors.
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.
Larbig
Gregor
G
Darmstadt Technical University, Clemens Schöpf-Institute for Organic Chemistry and Biochemistry, Petersenstrasse 22, D-64287 Darmstadt, Germany.
Schmidt
Boris
B
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases / Q000378:metabolism*; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000494:pharmacology
D005663:Furans; D011480:Protease Inhibitors; D011760:Pyrrolidinones; C009435:tetramic acid; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; C003422:tetronic acid