Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery
Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery
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DOI：
10.1021/ml400171b
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发表时间：
2013-08-01
影响因子：
4.2
通讯作者：
Wright, Adrian G.
中科院分区：
文献类型：
--
作者：
Czechtizky, Werngard;Dedio, Jueergen;Wright, Adrian G.
一个新的集成发现平台已被用于合成和生物测定一系列黄嘌呤衍生的二肽基肽酶4（DPP 4）拮抗剂。设计，合成，纯化，定量，稀释和生物测定都已完全集成，允许连续自动化操作。该系统已针对一组已知的DPP 4抑制剂进行了验证，并显示出传统药物化学生成的生物数据与平台数据之间具有良好的相关性。通过生物测定的合成的每个迭代循环总共花费两个小时，证明了快速迭代的结构-活性关系生成。
A novel integrated discovery platform has been used to synthesize and biologically assay a series of xanthine-derived dipeptidyl peptidase 4 (DPP4) antagonists. Design, synthesis, purification, quantitation, dilution, and bioassay have all been fully integrated to allow continuous automated operation. The system has been validated against a set of known DPP4 inhibitors and shown to give excellent correlation between traditional medicinal chemistry generated biological data and platform data. Each iterative loop of synthesis through biological assay took two hours in total, demonstrating rapid iterative structure-activity relationship generation.