Optimization of Selective and CNS Penetrant Alkyne-Based TREK Inhibitors: The Discovery and Characterization of ONO-9517601 (VU6022856) and ONO-7927846 (VU6024391).

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Title: Optimization of Selective and CNS Penetrant Alkyne-Based TREK Inhibitors: The Discovery and Characterization of ONO-9517601 (VU6022856) and ONO-7927846 (VU6024391).
Authors: Tanaka M; Drug Discovery Chemistry, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan., Sekioka Y; Research Center of Neurology, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan., Hashimoto G; Research Center of Neurology, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan., Mori T; Research Center of Neurology, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan., Shono T; Pharmacokinetic Research, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan., Isaji Y; Safety Research, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan., Hisaichi K; Drug Discovery Chemistry, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan., Childress ES; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Bollinger S; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Schmitt JA; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Chopko TC; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Garrison AT; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Perry CK; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Chronister K; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Kramer M; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Chang S; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Watson KJ; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Dickerson JW; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Bubser M; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Rook JM; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Jones CK; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Boutaud O; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Bridges TM; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Denton JS; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States., Engers DW; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Kurata H; Drug Discovery Chemistry, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan., Lindsley CW; Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
Source: Journal of medicinal chemistry [J Med Chem] 2025 Nov 13; Vol. 68 (21), pp. 23554-23572. Date of Electronic Publication: 2025 Oct 17.
Publication Type: Journal Article
Journal Info: Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE
Database: MEDLINE Ultimate
Description
ISSN:1520-4804
DOI:10.1021/acs.jmedchem.5c02535