Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery
- Werngard Czechtizky
- Jurgen Dedio
- Bimbisar Desai
- Karen Dixon
- Elizabeth Farrant
- Qixing Feng Trevor Morgen
- David M Parry
- Manoj K. Ramjee
- Christopher N. Selway
- Thorsten Schmidt
- Gary J. Tarver
- Adrian G. Wright
- Sanofi-Aventis, Frankfurt, Germany. Cyclofluidic Ltd., U.K.Read the publication that featured this abstract
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.
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