Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593082 | Bioorganic & Medicinal Chemistry Letters | 2012 | 5 Pages |
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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Authors
Suzanne S. Stokes, Madhusudhan Gowravaram, Hoan Huynh, Min Lu, George B. Mullen, Brendan Chen, Robert Albert, Thomas J. O'Shea, Michael T. Rooney, Haiqing Hu, Joseph V. Newman, Scott D. Mills,