Thiophene inhibitors of PDE4: crystal structures show a second binding mode at the catalytic domain of PDE4D2

Jacob Nankervis, Susanne Feil, Nancy Hancock, Zhaohua Zheng, Hooi-ling Ng, Craig Morton, Jessica Holien, Patricia Ho, Mark Frazzetto, Ian Jennings, David Manallack, T John Martin, Philip Thompson, Michael Parker

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16 Citations (Scopus)


PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor. (C) 2011 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)7089 - 7093
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number23
Publication statusPublished - 2011

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