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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors.
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Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors.

机译：新型金黄色葡萄球菌分选酶A抑制剂的合成及其结构活性关系的研究。

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摘要

Synthetic methods have been developed for lead Sortase A inhibitors identified from previous studies. Several derivatives of the lead inhibitor were synthesized to derive preliminary structure activity relationships (SAR). Different regions of the lead inhibitor that are critical for the enzyme activity have been determined by systematic SAR studies. The E stereochemistry of the lead compound was found to be critical for its activity. Replacement of the E double bond with Z double bond or a rigid triple bond reduced the enzyme inhibitory activity in most cases. Reduction of the double bond to a C-C single bond resulted in complete loss of activity. Amide carbonyl and NH groups were also found to be crucial for the activity of this class of inhibitors, as well. The morpholine ring oxygen atom was also found to be an important factor for the activity of the lead inhibitor. Preliminary SAR studies led to the identification of compounds with improved enzyme inhibition. The most active compound was found to have an IC(50) value of 58 microM against the enzyme.
机译：已经开发了用于从先前研究中鉴定的先导分选酶A抑制剂的合成方法。合成了铅抑制剂的几种衍生物以得到初步的结构活性关系（SAR）。通过系统的SAR研究已经确定了对酶活性至关重要的铅抑制剂的不同区域。发现铅化合物的E立体化学对其活性至关重要。在大多数情况下，用Z双键或刚性三键替换E双键会降低酶的抑制活性。双键还原为C-C单键导致活性完全丧失。还发现酰胺羰基和NH基团对于这类抑制剂的活性也至关重要。还发现吗啉环氧原子是铅抑制剂活性的重要因素。 SAR的初步研究导致鉴定出具有改善的酶抑制作用的化合物。发现活性最高的化合物对该酶的IC（50）值为58 microM。

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