Discovery of a New Class of Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B by Biology‐Oriented Synthesis

Abstract

A biologically relevant collection: The synthesis of a macroline‐derived compound collection (see general structural formula) on the basis of the criterion of biological relevance yielded an unprecedented class of inhibitors of the title mycobacterial enzyme, which is a potential target for the development of new antimycobacterial drug candidates.

Principles, implementation, and application of biology-oriented synthesis (BIOS)

“…By extending the screen to other phosphatases, structurally new inhibitors of the Mycobacterium tuberculosis phosphatase MptpB could be identified (Nören-Müller et al, 2006;Corrêa et al, 2007). In a similar manner, BIOS of a focused library of macroline analogs, several new inhibitors of the Mycobacterium tuberculosis phosphatase MptpB were also found (Nören-Müller et al, 2008;Wilk et al, 2009a). Macrolines are a class of natural products to which secondary metabolites such as Rauwolfia serpentina alkaloid and antiarrhythmic agent Ajmaline belong.…”

The Chiral Pool in the Pictet–Spengler Reaction for the Synthesis of β-Carbolines

“…However, under these conditions the racemization of the products was possible [22]. By this methodology, besides the application of Cook's group to the preparation of natural products [18,[23][24][25][26][27][28], a new class of inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B was synthesized by Waldmann and co-workers [29].…”

An Expedient General Synthesis of Quinolino and Pyrrolocycloocta[b] Indoles

“…The diverse biological activities of these alkaloids validate the cycloocta [b]indole core ( Figure 2) as a promising scaffold for the generation of bioactive compounds. Compounds containing a quinoline framework have been found applications as pharmaceuticals and agrochemicals, as well as being general synthetic building blocks [8][9][10]. Industrial, biological, and synthetic significance places this scaffold in a prestigious position.…”