Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wrocław, Poland.
J Med Chem. 2010 Aug 12;53(15):5597-606. doi: 10.1021/jm100340m.
Urease inhibitors can be considered as a tool to control the damaging effect of ureolytic bacteria infections in humans which occur commonly in the developed countries. Computer-aided optimization of the aminomethylphosphinate structures by modifying both their N- and P-termini led to the invention of a novel group of inhibitors of bacterial ureases. Introduction of P-hydroxymethyl group into the molecule resulted in considerable increase of the inhibitory activity against enzymes purified from Bacillus pasteurii and Proteus vulgaris as compared with their P-methyl counterparts described previously. The designed compounds represent a competitive reversible class of urease inhibitors. The most potent, N-methyl-aminomethyl-P-hydroxymethylphosphinic acid, displayed K(i) = 360 nM against P. vulgaris enzyme.
脲酶抑制剂可以被认为是一种控制人类脲酶细菌感染破坏性影响的工具，这种感染在发达国家很常见。通过修饰氨基甲基膦酸的 N-和 P-末端，对其结构进行计算机辅助优化，从而发明了一类新型的细菌脲酶抑制剂。在分子中引入 P-羟甲基基团，与以前描述的 P-甲基类似物相比，可显著提高对巴氏芽孢杆菌和普通变形杆菌中纯化酶的抑制活性。所设计的化合物代表了一类具有竞争力的可逆脲酶抑制剂。最有效的抑制剂为 N-甲基-氨基甲基-P-羟甲基膦酸，对普通变形杆菌酶的 K(i)值为 360 nM。
