7-Alkyl-N(2)-substituted-3-deazaguanines. Synthesis, DNA polymerase III inhibition and antibacterial activity.
7-Alkyl-N(2)-substituted-3-deazaguanines. Synthesis, DNA polymerase III inhibition and antibacterial activity.
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7-烷基-N(2)-取代-3-脱氮鸟嘌呤。
DOI：
10.1016/j.bmcl.2011.05.093
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发表时间：
2011
影响因子：
2.7
通讯作者：
Butler,MichelleM
中科院分区：
文献类型：
--
作者：
Xu,Wei-Chu;Wright,GeorgeE;Brown,NealC;Long,Zheng-Yu;Zhi,Cheng-Xin;Dvoskin,Sofya;Gambino,JosephJ;Barnes,MarjorieH;Butler,MichelleM
已经合成了几种2-苯胺基-和2-苄氨基-3-脱氮杂-6-氧代嘌呤[3-脱氮鸟嘌呤]以及选定的8-甲基和8-氮杂类似物。 7-取代的N2-(3-乙基-4-甲基苯基)-3-脱氮鸟嘌呤是革兰氏+细菌DNA聚合酶(pol) IIIC的有效和选择性抑制剂，7-取代的N2-(3,4-二氯苄基)-3-脱氮鸟嘌呤是革兰氏+细菌的pol IIIC和pol IIIE的有效抑制剂，但对革兰氏-细菌的pol IIIE有微弱的抑制作用。两类强效酶抑制剂均能抑制革兰氏阳性细菌的生长（MIC 2.5–10μg/ml），并且对革兰氏阴性大肠杆菌没有活性。几种衍生物对金黄色葡萄球菌感染的小鼠具有中等的保护活性。
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 2.5–10 μg/ml), and were inactive against the Gram− organismEscherichia coli. Several derivatives had moderate protective activity in Staphylococcus aureus-infected mice.