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). |
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| 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 |
| FullText | Text: Availability: 0 |
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| Header | DbId: mdl DbLabel: MEDLINE Ultimate An: 41104520 AccessLevel: 2 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Optimization of Selective and CNS Penetrant Alkyne-Based TREK Inhibitors: The Discovery and Characterization of ONO-9517601 (VU6022856) and ONO-7927846 (VU6024391). – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AU" term="%22Tanaka+M%22">Tanaka M</searchLink>; Drug Discovery Chemistry, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.<br /><searchLink fieldCode="AU" term="%22Sekioka+Y%22">Sekioka Y</searchLink>; Research Center of Neurology, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.<br /><searchLink fieldCode="AU" term="%22Hashimoto+G%22">Hashimoto G</searchLink>; Research Center of Neurology, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.<br /><searchLink fieldCode="AU" term="%22Mori+T%22">Mori T</searchLink>; Research Center of Neurology, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.<br /><searchLink fieldCode="AU" term="%22Shono+T%22">Shono T</searchLink>; Pharmacokinetic Research, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.<br /><searchLink fieldCode="AU" term="%22Isaji+Y%22">Isaji Y</searchLink>; Safety Research, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.<br /><searchLink fieldCode="AU" term="%22Hisaichi+K%22">Hisaichi K</searchLink>; Drug Discovery Chemistry, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.<br /><searchLink fieldCode="AU" term="%22Childress+ES%22">Childress ES</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Bollinger+S%22">Bollinger S</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Schmitt+JA%22">Schmitt JA</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Chopko+TC%22">Chopko TC</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Garrison+AT%22">Garrison AT</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Perry+CK%22">Perry CK</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Chronister+K%22">Chronister K</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Kramer+M%22">Kramer M</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Chang+S%22">Chang S</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Watson+KJ%22">Watson KJ</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Dickerson+JW%22">Dickerson JW</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Bubser+M%22">Bubser M</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Rook+JM%22">Rook JM</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Jones+CK%22">Jones CK</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Boutaud+O%22">Boutaud O</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Bridges+TM%22">Bridges TM</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Denton+JS%22">Denton JS</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Engers+DW%22">Engers DW</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Kurata+H%22">Kurata H</searchLink>; Drug Discovery Chemistry, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan.<br /><searchLink fieldCode="AU" term="%22Lindsley+CW%22">Lindsley CW</searchLink>; 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. – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%229716531%22">Journal of medicinal chemistry</searchLink> [J Med Chem] 2025 Nov 13; Vol. 68 (21), pp. 23554-23572. <i>Date of Electronic Publication: </i>2025 Oct 17. – Name: TypePub Label: Publication Type Group: TypPub Data: Journal Article – Name: TitleSource Label: Journal Info Group: Src Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22American+Chemical+Society%22">American Chemical Society </searchLink><i>Country of Publication: </i>United States <i>NLM ID: </i>9716531 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1520-4804 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2200222623%22">00222623 </searchLink><i>NLM ISO Abbreviation: </i>J Med Chem <i>Subsets: </i>MEDLINE |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1021/acs.jmedchem.5c02535 Languages: – Code: eng Text: English PhysicalDescription: Pagination: StartPage: 23554 Titles: – TitleFull: Optimization of Selective and CNS Penetrant Alkyne-Based TREK Inhibitors: The Discovery and Characterization of ONO-9517601 (VU6022856) and ONO-7927846 (VU6024391). Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Tanaka M – PersonEntity: Name: NameFull: Sekioka Y – PersonEntity: Name: NameFull: Hashimoto G – PersonEntity: Name: NameFull: Mori T – PersonEntity: Name: NameFull: Shono T – PersonEntity: Name: NameFull: Isaji Y – PersonEntity: Name: NameFull: Hisaichi K – PersonEntity: Name: NameFull: Childress ES – PersonEntity: Name: NameFull: Bollinger S – PersonEntity: Name: NameFull: Schmitt JA – PersonEntity: Name: NameFull: Chopko TC – PersonEntity: Name: NameFull: Garrison AT – PersonEntity: Name: NameFull: Perry CK – PersonEntity: Name: NameFull: Chronister K – PersonEntity: Name: NameFull: Kramer M – PersonEntity: Name: NameFull: Chang S – PersonEntity: Name: NameFull: Watson KJ – PersonEntity: Name: NameFull: Dickerson JW – PersonEntity: Name: NameFull: Bubser M – PersonEntity: Name: NameFull: Rook JM – PersonEntity: Name: NameFull: Jones CK – PersonEntity: Name: NameFull: Boutaud O – PersonEntity: Name: NameFull: Bridges TM – PersonEntity: Name: NameFull: Denton JS – PersonEntity: Name: NameFull: Engers DW – PersonEntity: Name: NameFull: Kurata H – PersonEntity: Name: NameFull: Lindsley CW IsPartOfRelationships: – BibEntity: Dates: – D: 13 M: 11 Text: 2025 Nov 13 Type: published Y: 2025 Identifiers: – Type: issn-electronic Value: 1520-4804 Numbering: – Type: volume Value: 68 – Type: issue Value: 21 Titles: – TitleFull: Journal of medicinal chemistry Type: main |
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