title: Integrated Synthesis and Testing of Substituted Xanthine Based DPP4 Inhibitors: Application to Drug Discovery.
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.
authors.affiliation: Sanofi-Aventis , Industriepark Höchst, Gebäude K703, 65929 Frankfurt, Germany.
authors.forename: Werngard
authors.initials: W
authors.lastname: Czechtizky
authors.affiliation: Sanofi-Aventis , Industriepark Höchst, Gebäude K703, 65929 Frankfurt, Germany.
authors.forename: Jüergen
authors.initials: J
authors.lastname: Dedio
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: Bimbisar
authors.initials: B
authors.lastname: Desai
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: Karen
authors.initials: K
authors.lastname: Dixon
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Farrant
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: Qixing
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: Trevor
authors.initials: T
authors.lastname: Morgan
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: David M
authors.initials: DM
authors.lastname: Parry
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Ramjee
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Selway
authors.affiliation: Sanofi-Aventis , Industriepark Höchst, Gebäude K703, 65929 Frankfurt, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Tarver
authors.affiliation: Cyclofluidic Ltd. , Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, U.K.
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Wright
keywords: Closed loop drug design; DPP4; automated drug discovery; flow synthesis