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ID: ALA2029313

Journal: Bioorg Med Chem Lett

Title: Design, synthesis and biological evaluation of potent NAD+-dependent DNA ligase inhibitors as potential antibacterial agents. Part I: aminoalkoxypyrimidine carboxamides.

Authors: Gu W, Wang T, Maltais F, Ledford B, Kennedy J, Wei Y, Gross CH, Parsons J, Duncan L, Arends SJ, Moody C, Perola E, Green J, Charifson PS.

Abstract: A series of 2,6-disubstituted aminoalkoxypyrimidine carboxamides (AAPCs) with potent inhibition of bacterial NAD(+)-dependent DNA ligase was discovered through the use of structure-guided design. Two subsites in the NAD(+)-binding pocket were explored to modulate enzyme inhibitory potency: a hydrophobic selectivity region was explored through a series of 2-alkoxy substituents while the sugar (ribose) binding region of NAD(+) was explored via 6-alkoxy substituents.

CiteXplore: 22560473

DOI: 10.1016/j.bmcl.2012.04.037