Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Org Biomol Chem. 2010 Sep 21;8(18):4066-70. doi: 10.1039/c0ob00182a. Epub 2010 Jul 19.
The design and synthesis of new inhibitor analogues for the Mycobacterium tuberculosis (Mtb) phosphatase PtpB is described. Analogues were synthesized by incorporation of two common and effective phosphate mimetics, the isothiazolidinone (IZD) and the difluoromethylphosphonic acid (DFMP). The basic scaffold of the inhibitor was identified from structure-activity relationships established for a previously published isoxazole inhibitor, while the phosphate mimetics were chosen based on their proven cell permeability and activity when incorporated into previously reported inhibitors for the phosphatase PTP1B. The inhibitory activity of each compound was evaluated, and each was found to have low or submicromolar affinity for PtpB.
本文描述了结核分枝杆菌（Mtb）磷酸酶 PtpB 的新型抑制剂类似物的设计和合成。通过引入两种常见且有效的磷酸类似物——异噻唑啉酮（IZD）和二氟膦酸（DFMP）来合成类似物。抑制剂的基本骨架是根据先前发表的异噁唑抑制剂的构效关系确定的，而磷酸类似物则是根据它们在先前报道的磷酸酶 PTP1B 抑制剂中的细胞通透性和活性选择的。评估了每个化合物的抑制活性，发现它们对 PtpB 的亲和力均较低或亚微摩尔级。
