Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery

作者：Werngard Czechtizky, Jüergen Dedio, Bimbisar K. Desai, Karen Dixon, Elizabeth Farrant, Qixing Feng, Trevor Morgan, David M. Parry, Manoj K. Ramjee, Christopher N. Selway, Thorsten Schmidt, Gary J. Tarver, Adrian G. Wright · 发表于：ACS Medicinal Chemistry Letters · 年份：2013 · DOI：10.1021/ml400171b · 被引用次数：64 · 研究领域：Peptidase Inhibition and Analysis、Chemical Synthesis and Analysis、Biochemical and Molecular Research

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.