作为β-分泌酶抑制剂的四嗪酸和四酮酸的合成。

Synthesis of tetramic and tetronic acids as beta-secretase inhibitors.

作者信息

Larbig Gregor, Schmidt Boris

机构信息

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

出版信息

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

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.

摘要

天冬氨酸蛋白酶β-分泌酶（BACE-1）是治疗阿尔茨海默病的一个有吸引力的靶点。已知的抑制剂与底物肽具有高度相似性，因此表现出不良的药理特性。紧凑的非肽类先导结构很少见。在此，我们报道了特窗酸和四嗪酸对BACE-1抑制的活性。这些化合物具有低分子量和紧凑的骨架，可通过固相支持的多样合成获得。

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