Laura McDowell
Pfizer
9 Papers
9 Citations
Laura McDowell is an academic researcher from Pfizer. The author has contributed to research in topics: Histamine & Allosteric regulation. The author has an hindex of 8, co-authored 9 publications.
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Papers
The 5-hydroxytryptamine4 receptor agonists prucalopride and PRX-03140 increase acetylcholine and histamine levels in the rat prefrontal cortex and the power of stimulated hippocampal θ oscillations.
David E. Johnson,Elena M. Drummond,Sarah Grimwood,Aarti Sawant-Basak,Emily Miller,Elaine E. Tseng,Laura McDowell,Michelle Vanase-Frawley,Katherine Fisher,David M. Rubitski,Kim Jonelle Stutzman-Engwall,Robin T. Nelson,Weldon Horner,Roxanne R Gorczyca,Mihály Hajós,Chester J. Siok +15 more
TL;DR: Findings show for the first time that the 5-HT4 receptor agonists prucalopride and PRX-03140 can increase cortical ACh and histamine levels, augment donepezil-induced ACh increases, and increase stimulated-hippocampal θ power, all neuropharmacological parameters consistent with potential positive effects on cognitive processes.
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Use of structure-based design to discover a potent, selective, in vivo active phosphodiesterase 10A inhibitor lead series for the treatment of schizophrenia.
Christopher John Helal,Zhijun Kang,Xinjun Hou,Jayvardhan Pandit,Thomas Allen Chappie,John M. Humphrey,Eric S. Marr,Kimberly F. Fennell,Lois K. Chenard,Carol B. Fox,Christopher J. Schmidt,Robert D. Williams,Douglas S. Chapin,Judith A. Siuciak,Lorraine A. Lebel,Frank S. Menniti,Julia Cianfrogna,Kari R. Fonseca,Frederick R. Nelson,Rebecca E. O’Connor,Mary C. MacDougall,Laura McDowell,Spiros Liras +22 more
TL;DR: A novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes by utilizing structure-based virtual library design and scoring.
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Characterization of substrate binding and catalysis in the potential antibacterial target N‐acetylglucosamine‐1‐phosphate uridyltransferase (GlmU)
Igor Mochalkin,Sandra Lightle,Yaqi Zhu,Jeffrey F. Ohren,Cindy Spessard,Nickolay Y. Chirgadze,Nickolay Y. Chirgadze,Nickolay Y. Chirgadze,Craig Banotai,Michael Melnick,Laura McDowell +10 more
TL;DR: The new data strongly suggest that the mechanism of phosphotransfer in the uridyltransferase reaction in GlmU is primarily through an associative mechanism with a pentavalent phosphate intermediate and an inversion of stereochemistry.
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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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