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

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• 作者：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
• 关键词：M. tuberculosis ; Enoyl-ACP reductase (InhA) ; NAD analogues ; Isoniazid ; Fragment-based drug discovery
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 August 2007
• 卷：17
• 期：16
• 页码：4588-4591
• 文件大小：522 K

摘要

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.