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Identification of Inhibitors for Mycobacterial Protein Tyrosine Phosphatase B (MptpB) by Biology‐Oriented Synthesis (BIOS)
Author(s) -
Corrêa Ivan R.,
NörenMüller Andrea,
Ambrosi HorstDieter,
Jakupovic Sven,
Saxena Krishna,
Schwalbe Harald,
Kaiser Markus,
Waldmann Herbert
Publication year - 2007
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200700125
Subject(s) - phosphatase , protein tyrosine phosphatase , chemical biology , biochemistry , chemistry , identification (biology) , protein phosphatase 2 , biology , combinatorial chemistry , enzyme , computational biology , botany
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.