Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis

Laurent Bonnac, Guang Yao Gao, Liqiang Chen, Krzysztof Felczak, Eric M. Bennett, Hua Xu, Tae Soo Kim, Nina Liu, Hye Won Oh, Peter J. Tonge, Krzysztof W. Pankiewicz

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The chemical synthesis of 4-phenoxybenzamide adenine dinucleotide (3), a NAD analogue which mimics isoniazid-NAD adduct and inhibits Mycobacterium tuberculosis NAD-dependent enoyl-ACP reductase (InhA), is reported. The 4-phenoxy benzamide riboside (1) has been prepared as a key intermediate, converted into its 5′-mononucleotide (2), and coupled with AMP imidazolide to give the desired NAD analogue 3. It inhibits InhA with IC50 = 27 μM.

Original languageEnglish (US)
Pages (from-to)4588-4591
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number16
DOIs
StatePublished - Aug 15 2007

Keywords

  • Enoyl-ACP reductase (InhA)
  • Fragment-based drug discovery
  • Isoniazid
  • M. tuberculosis
  • NAD analogues

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Bonnac, L., Gao, G. Y., Chen, L., Felczak, K., Bennett, E. M., Xu, H., Kim, T. S., Liu, N., Oh, H. W., Tonge, P. J., & Pankiewicz, K. W. (2007). Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis. Bioorganic and Medicinal Chemistry Letters, 17(16), 4588-4591. https://doi.org/10.1016/j.bmcl.2007.05.084