Discovery of bacterial NAD+-dependent DNA ligase inhibitors: optimization of antibacterial activity

…, R Albert, M Cavero-Tomas, B Chen, J Harang…

Index: Stokes, Suzanne S.; Huynh, Hoan; Gowravaram, Madhusudhan; Albert, Robert; Cavero-Tomas, Marta; Chen, Brendan; Harang, Jenna; Loch III, James T.; Lu, Min; Mullen, George B.; Zhao, Shannon; Liu, Ce-Feng; Mills, Scott D. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 15 p. 4556 - 4560 Title/Abstract Full Text View citing articles Show Details Stokes, Suzanne S.; Gowravaram, Madhusudhan; Huynh, Hoan; Lu, Min; Mullen, George B.; Chen, Brendan; Albert, Robert; O'Shea, Thomas J.; Rooney, Michael T.; Hu, Haiqing; Newman, Joseph V.; Mills, Scott D. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 1 p. 85 - 89

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Citation Number: 21

Abstract

Optimization of adenosine analog inhibitors of bacterial NAD+-dependent DNA ligase is discussed. Antibacterial activity against Streptococcus pneumoniae and Staphylococcus aureus was improved by modification of the 2-position substituent on the adenine ring and 3′-and 5′-substituents on the ribose. Compounds with logD values 1.5–2.5 maximized potency and maintained drug-like physical properties.