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J-GLOBAL ID：201802275724164390   整理番号：18A0336697

M_4PAM in vivoツール化合物の開発における挑戦:近い類似体のVU0467154と予想外DMPKプロファイルの発見【Powered by NICT】

Challenges in the development of an M₄ PAM in vivo tool compound: The discovery of VU0467154 and unexpected DMPK profiles of close analogs

著者 (36件)： Wood Michael R. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Wood Michael R. (Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA) ,  Noetzel Meredith J. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Noetzel Meredith J. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Poslusney Michael S. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Melancon Bruce J. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Melancon Bruce J. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Tarr James C. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Lamsal Atin (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Chang Sichen (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Luscombe Vincent B. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Luscombe Vincent B. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Weiner Rebecca L. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Weiner Rebecca L. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Cho Hyekyung P. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Cho Hyekyung P. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Bubser Michael (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Jones Carrie K. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Jones Carrie K. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Jones Carrie K. (Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Niswender Colleen M. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Niswender Colleen M. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Niswender Colleen M. (Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Wood Michael W. (Neuroscience Innovative Medicines, Astra Zeneca, 141 Portland Street, Cambridge, MA 02139, USA) ,  Engers Darren W. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Engers Darren W. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Brandon Nicholas J. (Neuroscience Innovative Medicines, Astra Zeneca, 141 Portland Street, Cambridge, MA 02139, USA) ,  Duggan Mark E. (Neuroscience Innovative Medicines, Astra Zeneca, 141 Portland Street, Cambridge, MA 02139, USA) ,  Conn P. Jeffrey (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Conn P. Jeffrey (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Conn P. Jeffrey (Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Bridges Thomas M. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Bridges Thomas M. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Lindsley Craig W. (Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA) ,  Lindsley Craig W. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA) ,  Lindsley Craig W. (Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA)
資料名： Bioorganic & Medicinal Chemistry Letters  (Bioorganic & Medicinal Chemistry Letters)
巻： 27  号： 2  ページ： 171-175  発行年： 2017年 
JST資料番号： W0248A  ISSN： 0960-894X  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 5-アミノ-チエノ[2,3-c]ピリダジンコアに基づく新しい一連M_4陽性アロステリックモジュレーター(PAM)の化学的最適化,反復並列合成による開発を述べ,高利用げっ歯類のin vivoツール化合物,VU0467154(5)に至る。VU0467154の発見をもたらすことを最適化キャンペーン(SARとDMPKプロファイリング)の最初の報告であり,アロステリック調節因子プログラム(急SAR,PAM薬理学における種差とCNS浸透に影響する微妙な構造変化)の直面する課題の全てを詳述した。Copyright 2018 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【Powered by NICT】

シソーラス用語： 構造活性相関 ,  齧歯類 ,  浸透 ,  薬理学 ,  種差 ,  最適化 ,  *類似物質
準シソーラス用語： 構造変化 ,  プロファイリング , 【Automatic Indexing@JST】

著者キーワード (5件)： M_4 ,  ムスカリン性アセチルコリン受容体 ,  陽性アロステリックモジュレーター(PAM) ,  統合失調症 ,  構造活性相関(SAR)

分類 (2件)： 薬物の構造活性相関  (GV01050B) ,  ピリジンのその他の縮合誘導体  (CF07097Y)

タイトルに関連する用語 (7件)： ツール ,  開発 ,  類似体 ,  予想 ,  DMPK ,  プロファイル ,  発見