19813-35-5Relevant articles and documents
Identification of Morpholino Thiophenes as Novel Mycobacterium tuberculosis Inhibitors, Targeting QcrB
Cleghorn, Laura A. T.,Ray, Peter C.,Odingo, Joshua,Kumar, Anuradha,Wescott, Heather,Korkegian, Aaron,Masquelin, Thierry,Lopez Moure, Abraham,Wilson, Caroline,Davis, Susan,Huggett, Margaret,Turner, Penelope,Smith, Alasdair,Epemolu, Ola,Zuccotto, Fabio,Riley, Jennifer,Scullion, Paul,Shishikura, Yoko,Ferguson, Liam,Rullas, Joaquin,Guijarro, Laura,Read, Kevin D.,Green, Simon R.,Hipskind, Phil,Parish, Tanya,Wyatt, Paul G.
, p. 6592 - 6608 (2018)
With the emergence of multidrug-resistant strains of Mycobacterium tuberculosis there is a pressing need for new oral drugs with novel mechanisms of action. Herein, we describe the identification of a novel morpholino-thiophenes (MOT) series following phenotypic screening of the Eli Lilly corporate library against M. tuberculosis strain H37Rv. The design, synthesis, and structure-activity relationships of a range of analogues around the confirmed actives are described. Optimized leads with potent whole cell activity against H37Rv, no cytotoxicity flags, and in vivo efficacy in an acute murine model of infection are described. Mode-of-action studies suggest that the novel scaffold targets QcrB, a subunit of the menaquinol cytochrome c oxidoreductase, part of the bc1-aa3-type cytochrome c oxidase complex that is responsible for driving oxygen-dependent respiration.
The first synthesis of N-alkyl-N-arylthiocarbamoylacetates and acetic acids
Spears, Glen W.,Tsuji, Kiyoshi,Tojo, Takashi,Nishimura, Hiroaki,Ogino, Takashi
, p. 565 - 574 (2007/10/03)
N-Alkyl-N-arylthiocarbamoylacetates, the key intermediates for the synthesis of novel antinephritic agents, have been prepared for the first time. Some of the esters were in turn hydrolyzed to the corresponding acids. An alternative, indirect synthetic route was also developed to prepare some unusual acids.
