Synthesis and evaluation of nitrofuranylamides as novel antituberculosis agents

Rajendra P. Tangallapally, Raghunandan Yendapally, Robin E. Lee, Kirk Hevener, Victoria C. Jones, Anne J.M. Lenaerts, Michael R. McNeil, Yuehong Wang, Scott Franzblau, Richard E. Lee

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

In an effort to develop new and more potent therapies to treat tuberculosis, a library of compounds was screened for M. tuberculosis UDP-Gal mutase inhibition. Nitrofuranylamide 1 was identified as a hit in this screen, possessing good antituberculosis activity. This paper describes the synthesis and evaluation of an expanded set of nitrofuranylamides. We have discovered a number of nitrofuranylamides with submicromolar M. tuberculosis MIC values and acceptable therapeutic indexes. The MIC activity did not correlate with UDP-Gal mutase inhibition, suggesting an alternative primary cellular target was responsible for the antituberculosis activity. The compounds were only active against mycobacteria of the tuberculosis complex. On the basis of these results, four compounds were selected for in vivo testing in a mouse model of tuberculosis infection, and of these compounds one showed significant antituberculosis activity.

Original languageEnglish (US)
Pages (from-to)5276-5283
Number of pages8
JournalJournal of Medicinal Chemistry
Volume47
Issue number21
DOIs
StatePublished - Oct 7 2004

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Tuberculosis
Intramolecular Transferases
Uridine Diphosphate
Mycobacterium tuberculosis
Therapeutics
Infection

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Tangallapally, R. P., Yendapally, R., Lee, R. E., Hevener, K., Jones, V. C., Lenaerts, A. J. M., ... Lee, R. E. (2004). Synthesis and evaluation of nitrofuranylamides as novel antituberculosis agents. Journal of Medicinal Chemistry, 47(21), 5276-5283. https://doi.org/10.1021/jm049972y

Synthesis and evaluation of nitrofuranylamides as novel antituberculosis agents. / Tangallapally, Rajendra P.; Yendapally, Raghunandan; Lee, Robin E.; Hevener, Kirk; Jones, Victoria C.; Lenaerts, Anne J.M.; McNeil, Michael R.; Wang, Yuehong; Franzblau, Scott; Lee, Richard E.

In: Journal of Medicinal Chemistry, Vol. 47, No. 21, 07.10.2004, p. 5276-5283.

Research output: Contribution to journalArticle

Tangallapally, RP, Yendapally, R, Lee, RE, Hevener, K, Jones, VC, Lenaerts, AJM, McNeil, MR, Wang, Y, Franzblau, S & Lee, RE 2004, 'Synthesis and evaluation of nitrofuranylamides as novel antituberculosis agents', Journal of Medicinal Chemistry, vol. 47, no. 21, pp. 5276-5283. https://doi.org/10.1021/jm049972y
Tangallapally RP, Yendapally R, Lee RE, Hevener K, Jones VC, Lenaerts AJM et al. Synthesis and evaluation of nitrofuranylamides as novel antituberculosis agents. Journal of Medicinal Chemistry. 2004 Oct 7;47(21):5276-5283. https://doi.org/10.1021/jm049972y
Tangallapally, Rajendra P. ; Yendapally, Raghunandan ; Lee, Robin E. ; Hevener, Kirk ; Jones, Victoria C. ; Lenaerts, Anne J.M. ; McNeil, Michael R. ; Wang, Yuehong ; Franzblau, Scott ; Lee, Richard E. / Synthesis and evaluation of nitrofuranylamides as novel antituberculosis agents. In: Journal of Medicinal Chemistry. 2004 ; Vol. 47, No. 21. pp. 5276-5283.
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