Identification of inhibitors for mycobacterial protein tyrosine phosphatase B (MptpB) by biology-oriented synthesis (BIOS)

被引：59

作者：

Correa, Ivan R., Jr.

Noeren-Mueller, Andrea

Ambrosi, Horst-Dieter

Jakupovic, Sven

Saxena, Krishna

Schwalbe, Harald

Kaiser, Markus

Waldmann, Herbert

机构：

[1] Max Planck Inst Mol Physiol, Dept Biol Chem, D-44367 Dortmund, Germany

[2] Univ Dortmund, Facbereich 3, D-44367 Dortmund, Germany

[3] Hermannswerder Haus, AnalytiCon Discovery, D-14473 Potsdam, Germany

[4] Goethe Univ Frankfurt, Inst Organ Chem, D-60439 Frankfurt, Germany

[5] Max Planck Gesell, Chem Genom Ctr, D-44227 Dortmund, Germany

[6] Zentrum Angew Chem Genom BioMedZentrum Dortmund, D-44227 Dortmund, Germany

来源：

CHEMISTRY-AN ASIAN JOURNAL | 2007年 / 2卷 / 09期

关键词：

alkaloids; biology-oriented synthesis (BIOS); enzyme inhibition; phosphatases; solid-phase synthesis;

D O I：

10.1002/asia.200700125

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Protein phosphatases have recently emerged as important targets for research in chemical biology and medicinal chemistry, and new classes of phosphatase inhibitors are in high demand. BIOS (biology-oriented synthesis) employs the criteria of relevance to nature and biological prevalidation for the design and synthesis of compound collections. In an application of the BIOS principle, an efficient solid-phase synthesis of highly substituted indolo[2,3-a]quinolizidines by using a vinylogous Mannich-Michael reaction in combination with phosgene or acid-mediated ring closure was developed. Screening of this library for phosphatase inhibitors yielded a new inhibitor class for the Mycobacterium tuberculosis phosphatase MptpB.

引用

页码：1109 / 1126

页数：18

共 55 条

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