William E. Hoffman
Pfizer
4 Papers
William E. Hoffman is an academic researcher from Pfizer. The author has contributed to research in topics: Phosphodiesterase & Neuropharmacology. The author has an hindex of 4, co-authored 4 publications.
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Papers
Application of Structure-Based Design and Parallel Chemistry to Identify a Potent, Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor
Christopher John Helal,Eric P. Arnold,Tracey Boyden,Cheng Chang,Thomas Allen Chappie,Kimberly F. Fennell,Michael D. Forman,Mihály Hajós,John F. Harms,William E. Hoffman,John M. Humphrey,Zhijun Kang,Robin J. Kleiman,Bethany L. Kormos,Chewah Lee,Jiemin Lu,Noha Maklad,Laura McDowell,Scot Richard Mente,Rebecca E. O’Connor,Jayvardhan Pandit,Mary Piotrowski,Anne W. Schmidt,Christopher J. Schmidt,Hirokazu Ueno,Patrick Robert Verhoest,Edward X. Yang +26 more
TL;DR: The ability of PDE2A inhibitors to potentiate NMDA signaling and their further development for clinical cognition indications is supported by this data.
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Identification of a Potent, Highly Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor Clinical Candidate.
Christopher John Helal,Eric P. Arnold,Tracey Boyden,Cheng Chang,Thomas Allen Chappie,Ethan Lawrence Fisher,Mihály Hajós,John F. Harms,William E. Hoffman,John M. Humphrey,Jayvardhan Pandit,Zhijun Kang,Robin J. Kleiman,Bethany L. Kormos,Chewah Lee,Jiemin Lu,Noha Maklad,Laura McDowell,Dina McGinnis,Rebecca E. O’Connor,Christopher J. O’Donnell,Adam Ogden,Mary Piotrowski,Christopher J. Schmidt,Patricia A. Seymour,Hirokazu Ueno,Nichole Vansell,Patrick Robert Verhoest,Edward X. Yang +28 more
TL;DR: Computational modeling was used to direct the synthesis of analogs of previously reported phosphodiesterase 2A (PDE2A) inhibitor 1 with an imidazotriazine core to yield compounds of significantly enhanced potency that demonstrated potent binding to PDE2A in brain tissue and reversal of N-methyl-d-aspartate (NMDA) antagonist-induced effects in electrophysiology and working memory models in rats.
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Preclinical Characterization of Selective Phosphodiesterase 10A Inhibitors: A New Therapeutic Approach to the Treatment of Schizophrenia
Christopher J. Schmidt,Douglas S. Chapin,Julie Cianfrogna,M. L. Corman,Mihály Hajós,John F. Harms,William E. Hoffman,L. A. Lebel,Sheryl A. McCarthy,Fredrick R. Nelson,C. Proulx-LaFrance,Mark J. Majchrzak,Andres D. Ramirez,K. Schmidt,Patricia A. Seymour,Judith A. Siuciak,Francis David Tingley,R. D. Williams,Patrick Robert Verhoest,Frank S. Menniti +19 more
TL;DR: The discovery of a new class of PDE10A inhibitors exemplified by TP-10 (2-{4-[-pyridin-4-yl-1-(2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline succinic acid), an agent with greatly improved potency, selectivity, and pharmaceutical properties is described.
Application of Structure-Based Drug Design and Parallel Chemistry to Identify Selective, Brain Penetrant, In Vivo Active Phosphodiesterase 9A Inhibitors
Michelle Marie Claffey,Christopher John Helal,Patrick Robert Verhoest,Zhijun Kang,Kristina S. Fors,Stanley Jung,Jiaying Zhong,Mark W. Bundesmann,Xinjun Hou,Shenping Lui,Robin J. Kleiman,Michelle Vanase-Frawley,Anne W. Schmidt,Frank S. Menniti,Christopher J. Schmidt,William E. Hoffman,Mihály Hajós,Laura McDowell,Rebecca E. O’Connor,Mary MacDougall-Murphy,Kari R. Fonseca,Stacey L. Becker,Frederick R. Nelson,Spiros Liras +23 more
TL;DR: A novel series of PDE9A inhibitors was identified that showed improved selectivity over PDE1C that demonstrated free brain/free plasma ≥ 1 in rat and reduced microsomal clearance along with the ability to increase cyclic guanosine monophosphosphate levels in rat CSF.