Synthesis and evaluation of N-analogs of 1,2-diarylethane as Helicobacter pylori urease inhibitors.
Synthesis and evaluation of N-analogs of 1,2-diarylethane as Helicobacter pylori urease inhibitors.
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DOI：
10.1016/j.bmc.2015.06.014
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发表时间：
2015-08
影响因子：
3.5
通讯作者：
Zhu-Ping Xiao;Wei-Kang Shi;Peng‐Fei Wang;Wei Wei-Wei;Xiao-Tong Zeng;Ji-Rong Zhang;N. Zhu;M-J Peng-M-J-Pen
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文献类型：
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作者：
Zhu-Ping Xiao;Wei-Kang Shi;Peng‐Fei Wang;Wei Wei-Wei;Xiao-Tong Zeng;Ji-Rong Zhang;N. Zhu;M-J Peng-M-J-Pen
基于脲酶抑制的治疗方法现在被严肃地认为是幽门螺杆菌引起的感染的第一线治疗。然而，目前的抑制剂在高酸性胃液中无效或不稳定。在这里，我们报道了一系列苯基苯胺作为h的有效抑制剂。pyloriurease。在得到的21个化合物中，对N-（3,4-二羟基苄基）-4-硝基苯胺(4)进行了详细的评价，显示出作为抗羟基苯胺的发展前景。pyloriagent。在低浓度浓度下（IC50分别为0.62±0.04 μM和1.92±0.09 μM），无细胞提取液和完整细胞对脲酶均有较好的抑制作用，比阳性对照AHA分别提高29倍和54倍。SAR分析表明，4-甲氧基的3,4-二羟基的保护或4- no2的变化会导致效力的中等至急剧下降。
Therapies based on urease inhibition are now seriously considered as the first line of treatment for infections caused byHelicobacterpylori. However, the present inhibitors are ineffective or unstable in highly acidic gastric juice. Here, we report a series of benzylanilines as effective inhibitors ofH. pyloriurease. Out of the obtained twenty-one compounds,N-(3,4-dihydroxybenzyl)-4-nitroaniline (4) was evaluated in detail and shows promising features for development as anti-H. pyloriagent. Excellent potency against urease in both cell-free extract and intact cell was observed at low concentrations of4(IC50= 0.62 ± 0.04 and 1.92 ± 0.09 μM), which showed over 29- and 54-fold increase in potency with respect to the positive control AHA. The SAR analysis revealed that protection of 3,4-dihydroxy group of4as methoxy or changes of 4-NO2will result in a moderate to dramatic decrease in potency.