1. 7-Alkyl-N2-substituted-3-deazaguanines. Synthesis, DNA polymerase III inhibition and antibacterial activity
- Author
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Xu, Wei-chu, Wright, George E., Brown, Neal C., Long, Zheng-yu, Zhi, Cheng-xin, Dvoskin, Sofya, Gambino, Joseph J., Barnes, Marjorie H., and Butler, Michelle M.
- Subjects
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ANTIBACTERIAL agents , *DNA polymerases , *PURINES , *PHARMACEUTICAL chemistry , *ENZYME inhibitors , *GRAM-positive bacteria , *ORGANIC synthesis - Abstract
Abstract: Several 2-anilino- and 2-benzylamino-3-deaza-6-oxopurines [3-deazaguanines] and selected 8-methyl and 8-aza analogs have been synthesized. 7-Substituted N2-(3-ethyl-4-methylphenyl)-3-deazaguanines were potent and selective inhibitors of Gram+ bacterial DNA polymerase (pol) IIIC, and 7-substituted N2-(3,4-dichlorobenzyl)-3-deazaguanines were potent inhibitors of both pol IIIC and pol IIIE from Gram+ bacteria, but weakly inhibited pol IIIE from Gram− bacteria. Potent enzyme inhibitors in both classes inhibited the growth of Gram+ bacteria (MICs 2.5–10μg/ml), and were inactive against the Gram− organism Escherichia coli. Several derivatives had moderate protective activity in Staphylococcus aureus-infected mice. [Copyright &y& Elsevier]
- Published
- 2011
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