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

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 operatio...

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Veröffentlicht in:	ACS medicinal chemistry letters 2013-08, Vol.4 (8), p.768-772
Hauptverfasser:	Czechtizky, Werngard, Dedio, Jüergen, Desai, Bimbisar, Dixon, Karen, Farrant, Elizabeth, Feng, Qixing, Morgan, Trevor, Parry, David M, Ramjee, Manoj K, Selway, Christopher N, Schmidt, Thorsten, Tarver, Gary J, Wright, Adrian G
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Sprache:	eng
Schlagworte:	Letter
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container_title	ACS medicinal chemistry letters
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creator	Czechtizky, Werngard Dedio, Jüergen Desai, Bimbisar Dixon, Karen Farrant, Elizabeth Feng, Qixing Morgan, Trevor Parry, David M Ramjee, Manoj K Selway, Christopher N Schmidt, Thorsten Tarver, Gary J Wright, Adrian G
description	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.
doi_str_mv	10.1021/ml400171b
format	Article
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title	Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery
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