Corrêa, Ivan R.; Nören-Müller, Andrea; Ambrosi, Horst-Dieter; Jakupovic, Sven; Saxena, Krishna; Schwalbe, Harald; Kaiser, Markus; Waldmann, Herbert:

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

In: Chemistry : an Asian journal ; an ACES journal., Jg. 2 (2007) ; Nr. 9, S. 1109-1126
ISSN: 1861-4728
Zeitschriftenaufsatz / Fach: Biologie
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.