Design, synthesis and biological evaluation of potent NAD+-dependent DNA ligase inhibitors as potential antibacterial agents. Part 2: 4-Amino-pyrido [2, 3-d] pyrimidin …

…, L Duncan, W Gu, H O'Dowd, Y Wei, E Perola…

Index: Wang, Tiansheng; Duncan, Leonard; Gu, Wenxin; O'Dowd, Hardwin; Wei, Yunyi; Perola, Emanuele; Parsons, Jonathan; Gross, Christian H.; Moody, Cameron Stuver; Ryan Arends; Charifson, Paul S. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 11 p. 3699 - 3703

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Citation Number: 12

Abstract

The key binding determinants for the AAPC class include hydrogen bonds between: (1) the exocyclic pyrimidine amino group and the side chain carboxylate of Glu-118, (2) the carboxamide carbonyl oxygen and the backbone amide nitrogen of Ile-121, (3) the carboxamide nitrogen and the backbone carbonyl oxygen of Ile-121. Substitution at the 2-position with cycloalkoxy groups favorably complements the bacterial ligase-specific hydrophobic tunnel. 6 and 8 Based on these structural ...