双（氨甲基）次膦酸，一种极具潜力的用于开发细菌脲酶抑制剂的骨架。
Bis(aminomethyl)phosphinic Acid, a Highly Promising Scaffold for the Development of Bacterial Urease Inhibitors.
作者信息
Macegoniuk Katarzyna, Dziełak Anna, Mucha Artur, Berlicki Łukasz
机构信息
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
出版信息
ACS Med Chem Lett. 2014 Dec 11;6(2):146-50. doi: 10.1021/ml500380f. eCollection 2015 Feb 12.
Inhibitors of bacterial ureases are considered to be promising compounds in the treatment of infections caused by Helicobacter pylori in the gastric tract and/or by urealytic bacteria (e.g., Proteus species) in the urinary tract. A new, extended transition state scaffold, bis(aminomethyl)phosphinic acid, was successfully explored for the construction of effective enzyme inhibitors. A reliable methodology for the synthesis of phosphinate analogues in a three-component Mannich-type reaction was elaborated. The obtained molecules were assayed against ureases purified from Sporosarcina pasteurii and Proteus mirabilis, and aminomethyl(N-n-hexylaminomethyl)phosphinic acid was found to be the most potent inhibitor, with a K i = 108 nM against the S. pasteurii enzyme.
细菌脲酶抑制剂被认为是治疗由胃肠道幽门螺杆菌和/或泌尿道解脲脲原体（如变形杆菌属）引起的感染的有前景的化合物。一种新的、扩展的过渡态支架双（氨甲基）次膦酸已成功用于构建有效的酶抑制剂。阐述了一种在三组分曼尼希型反应中合成次膦酸酯类似物的可靠方法。对从巴氏芽孢八叠球菌和奇异变形杆菌中纯化的脲酶对所获得的分子进行了测定，发现氨甲基（N-正己基氨甲基）次膦酸是最有效的抑制剂，对巴氏芽孢八叠球菌脲酶的Ki = 108 nM。
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