University of Hertfordshire Research Archive

        JavaScript is disabled for your browser. Some features of this site may not work without it.

        Browse

        All of UHRABy Issue DateAuthorsTitlesThis CollectionBy Issue DateAuthorsTitles

        Arkivum Files

        My Downloads
        View Item 
        • UHRA Home
        • University of Hertfordshire
        • Research publications
        • View Item
        • UHRA Home
        • University of Hertfordshire
        • Research publications
        • View Item

        Library Design, Synthesis and Screening : Pyridine Dicarbonitriles as Potential Prion Disease Therapeutics

        Author
        Reddy, Tummala Rama Krishna
        Mutter, Roger
        Heal, William
        Guo, Kai
        Gillet, Valerie J.
        Pratt , Steven
        Chen, Beining
        Attention
        2299/10343
        Abstract
        Transmissible spongiform encephalopathies (TSEs) or prion diseases are a family of invariably fatal neurodegenerative disorders, and there are no effective therapeutics currently available. In this paper, we report on the design, synthesis, and screening of a series of pyridine dicarbonitriles as potential novel prion disease therapeutics. A virtual reaction-based library of 1050 compounds was constructed. Docking and evaluation using GOLD scores assisted the initial selection of compounds for synthesis. The selection was augmented with further compounds to increase structural diversity. A total of 45 compounds were synthesized via a one-pot three-component coupling reaction. The mechanism of the three-component coupling reaction was investigated, and it was discovered that chemical oxidation is required for the last step, forming the pyridine ring (aromatization). A total of 19 compounds were identified as binders to one or more forms of prion protein by in vitro screening using surface plasmon resonance (SPR). A selection of compounds were investigated for activity in cells, resulting in the discovery of a new inhibitor of PrPSc formation
        Publication date
        2006
        Published in
        Journal of Medicinal Chemistry
        Published version
        https://doi.org/10.1021/jm050610f
        Other links
        http://hdl.handle.net/2299/10343
        Metadata
        Show full item record
        Keep in touch

        © 2019 University of Hertfordshire

        I want to...

        • Apply for a course
        • Download a Prospectus
        • Find a job at the University
        • Make a complaint
        • Contact the Press Office

        Go to...

        • Accommodation booking
        • Your student record
        • Bayfordbury
        • KASPAR
        • UH Arts

        The small print

        • Terms of use
        • Privacy and cookies
        • Criminal Finances Act 2017
        • Modern Slavery Act 2015
        • Sitemap

        Find/Contact us

        • T: +44 (0)1707 284000
        • E: ask@herts.ac.uk
        • Where to find us
        • Parking
        • hr
        • qaa
        • stonewall
        • AMBA
        • ECU Race Charter
        • disability confident
        • AthenaSwan