Synthesis of tetramic and tetronic acids as beta-secretase inhibitors

Gregor Larbig; Boris Schmidt

doi:10.1021/cc0600021

Synthesis of tetramic and tetronic acids as beta-secretase inhibitors

J Comb Chem. 2006 Jul-Aug;8(4):480-90. doi: 10.1021/cc0600021.

Authors

Gregor Larbig¹, Boris Schmidt

Affiliation

¹ Darmstadt Technical University, Clemens Schöpf-Institute for Organic Chemistry and Biochemistry, Petersenstrasse 22, D-64287 Darmstadt, Germany.

PMID: 16827559
DOI: 10.1021/cc0600021

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy
Alzheimer Disease / enzymology
Amyloid Precursor Protein Secretases
Endopeptidases / metabolism*
Furans / chemical synthesis*
Furans / pharmacology
Molecular Structure
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / pharmacology
Pyrrolidinones / chemical synthesis*
Pyrrolidinones / pharmacology

Substances

Furans
Protease Inhibitors
Pyrrolidinones
tetramic acid
Amyloid Precursor Protein Secretases
Endopeptidases
tetronic acid