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 language | English (US) |
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Pages (from-to) | 4588-4591 |
Number of pages | 4 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 17 |
Issue number | 16 |
DOIs | |
State | Published - Aug 15 2007 |
Bibliographical note
Funding Information:These studies were funded by the Center for Drug Design, University of Minnesota. We thank the Minnesota Supercomputing Institute for computer time.
Keywords
- Enoyl-ACP reductase (InhA)
- Fragment-based drug discovery
- Isoniazid
- M. tuberculosis
- NAD analogues