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  • Title: Discovery of bacterial NAD⁺-dependent DNA ligase inhibitors: improvements in clearance of adenosine series.
    Author: Stokes SS, Gowravaram M, Huynh H, Lu M, Mullen GB, Chen B, Albert R, O'Shea TJ, Rooney MT, Hu H, Newman JV, Mills SD.
    Journal: Bioorg Med Chem Lett; 2012 Jan 01; 22(1):85-9. PubMed ID: 22154350.
    Abstract:
    Optimization of clearance of adenosine inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. To reduce Cytochrome P-450-mediated metabolic clearance, many strategies were explored; however, most modifications resulted in compounds with reduced antibacterial activity and/or unchanged total clearance. The alkyl side chains of the 2-cycloalkoxyadenosines were fluorinated, and compounds with moderate antibacterial activity and favorable pharmacokinetic properties in rat and dog were identified.
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