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
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 microM.
August 15, 2007: Bioorganic & Medicinal Chemistry Letters