title: Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis.
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 microM.
authors.affiliation: Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonnac
authors.forename: Guang-Yao
authors.initials: GY
authors.lastname: Gao
authors.forename: Liqiang
authors.initials: L
authors.lastname: Chen
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Felczak
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bennett
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: TaeSoo
authors.initials: T
authors.lastname: Kim
authors.forename: Nina
authors.initials: N
authors.lastname: Liu
authors.forename: HyeWon
authors.initials: H
authors.lastname: Oh
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Tonge
authors.forename: Krzysztof W
authors.initials: KW
authors.lastname: Pankiewicz
mesh_terms: D000227:Adenine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009243:NAD / Q000031:analogs & derivatives* / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000227:Adenine Nucleotides; D009243:NAD; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)