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, TaeSoo Kim, Nina Liu, HyeWon Oh, Peter J. Tonge, Krzysztof W. Pankiewicz

Research output: Contribution to journalArticle

14 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Adenine
Mycobacterium tuberculosis
NAD
Oxidoreductases
Isoniazid
Adenosine Monophosphate
Inhibitory Concentration 50

Keywords

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

ASJC Scopus subject areas

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

Cite this

Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis. / Bonnac, Laurent; Gao, Guang Yao; Chen, Liqiang; Felczak, Krzysztof; Bennett, Eric M.; Xu, Hua; Kim, TaeSoo; Liu, Nina; Oh, HyeWon; Tonge, Peter J.; Pankiewicz, Krzysztof W.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 16, 15.08.2007, p. 4588-4591.

Research output: Contribution to journalArticle

Bonnac, Laurent ; Gao, Guang Yao ; Chen, Liqiang ; Felczak, Krzysztof ; Bennett, Eric M. ; Xu, Hua ; Kim, TaeSoo ; Liu, Nina ; Oh, HyeWon ; Tonge, Peter J. ; Pankiewicz, Krzysztof W. / Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis. In: Bioorganic and Medicinal Chemistry Letters. 2007 ; Vol. 17, No. 16. pp. 4588-4591.
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AU - Bennett, Eric M.

AU - Xu, Hua

AU - Kim, TaeSoo

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