710351-24-9Relevant articles and documents
Design, synthesis, and evaluation of new thiadiazole-based direct inhibitors of enoyl acyl carrier protein reductase (InhA) for the treatment of tuberculosis
?ink, Roman,Sosi?, Izidor,?ivec, Matej,Fernandez-Menendez, Raquel,Turk, Samo,Pajk, Stane,Alvarez-Gomez, Daniel,Lopez-Roman, Eva Maria,Gonzales-Cortez, Carolina,Rullas-Triconado, Joaquin,Angulo-Barturen, Inigo,Barros, David,Ballell-Pages, Lluís,Young, Robert J.,Encinas, Lourdes,Gobec, Stanislav
supporting information, p. 613 - 624 (2015/01/30)
Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, a disease that still causes the death of at least a million people annually. A known class of potent, direct, and competitive InhA inhibitors based on a tetracyclic thiadiazole structure has been shown to have in vivo activity in murine models of tuberculosis infection. On the basis of this template, we have here explored the medicinal chemistry of truncated analogues that have only three aromatic rings. In particular, compounds 8b, 8d, 8f, 8l, and 8n show interesting features, including low nanomolar InhA IC50, submicromolar antimycobacterial potency, and improved physicochemical profiles in comparison with the tetracyclic analogues. From this series, 8d is identified as having the best balance of potency and properties, whereby the resolved 8d S-enatiomer shows encouraging in vivo efficacy.
Substituted benzazoles and methods of their use as inhibitors of Raf kinase
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Page 370, (2008/06/13)
New substituted benz-azole compounds, compositions and methods of inhibition of Raf kinase activity in a human or animal subject are provided. The new compounds compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.
