English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Decaprenylphosphoryl-β-d-ribose 2'-epimerase (DprE1) is an essential enzyme in Mycobacterium tuberculosis and has recently been studied as a potential drug target, with inhibitors progressing to clinical studies. Here we describe the identification of a novel series of morpholino-pyrimidine DprE1 inhibitors. These were derived from a phenotypic high-throughput screening (HTS) hit with suboptimal physicochemical properties. Optimization strategies included scaffold-hopping, synthesis, and evaluation of fragments of the lead compounds and property-focused optimization. The resulting optimized compounds had much improved physicochemical properties and maintained enzyme and cellular potency. These molecules demonstrated potent efficacy in an in vivo tuberculosis murine infection model.

journal of medicinal chemistry

<i>Mycobacterium tuberculosis</i> Decaprenylphosphoryl-β-<scp>d</scp>-ribose Oxidase Inhibitors: Expeditious Reconstruction of Suboptimal Hits into a Series with Potent in Vivo Activity

Mycobacterium tuberculosis Decaprenylphosphoryl-β-d-ribose Oxidase Inhibitors: Expeditious Reconstruction of Suboptimal Hits into a Series with Potent in Vivo Activity