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Chem Asian J. 2007 Sep 3;2(9):1109-26.

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

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  • 1Max Planck Institute of Molecular Physiology, Department of Chemical Biology, D-44367 Dortmund, Germany.


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.

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