Identification of inhibitors for mycobacterial protein tyrosine phosphatase B (MptpB) by biology-oriented synthesis (BIOS)
Identification of inhibitors for mycobacterial protein tyrosine phosphatase B (MptpB) by biology-oriented synthesis (BIOS)
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DOI：
10.1002/asia.200700125
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发表时间：
2007-01-01
影响因子：
4.1
通讯作者：
Waldmann, Herbert
中科院分区：
文献类型：
--
作者：
Correa, Ivan R., Jr.;Noeren-Mueller, Andrea;Waldmann, Herbert
蛋白磷酸酶最近已成为化学生物学和药物化学研究的重要目标，并且对新型磷酸酶抑制剂的需求很高。生物导向合成（biology-oriented synthesis，BIOS）采用与自然相关的标准和生物预验证来设计和合成化合物集合。在BIOS原理的应用中，开发了通过使用乙烯基Mannich-Michael反应结合光气或酸介导的闭环的高效固相合成高度取代的吲哚并[2，3-a]喹嗪烷的方法。筛选该文库的磷酸酶抑制剂产生了结核分枝杆菌磷酸酶MptpB的新抑制剂类。
Protein phosphatases have recently emerged as important targets for research in chemical biology and medicinal chemistry, and new classes of phosphatase inhibitors are in high demand. BIOS (biology-oriented synthesis) employs the criteria of relevance to nature and biological prevalidation for the design and synthesis of compound collections. In an application of the BIOS principle, an efficient solid-phase synthesis of highly substituted indolo[2,3-a]quinolizidines by using a vinylogous Mannich-Michael reaction in combination with phosgene or acid-mediated ring closure was developed. Screening of this library for phosphatase inhibitors yielded a new inhibitor class for the Mycobacterium tuberculosis phosphatase MptpB.