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J-GLOBAL ID：202202256397186820   整理番号：22A0972711

部分的グルコキナーゼ活性化因子臨床候補の発見:ジエチル((3-(3-((5-(アゼチジン-1-カルボニル)ピラジン-2-イル)オキシ)-5-イソプロポキシベンゾアミド)-1H-ピラゾール-1-イル)メチル)ホスホナート(BMS-820132)【JST・京大機械翻訳】

Discovery of a Partial Glucokinase Activator Clinical Candidate: Diethyl ((3-(3-((5-(Azetidine-1-carbonyl)pyrazin-2-yl)oxy)-5-isopropoxybenzamido)-1H-pyrazol-1-yl)methyl)phosphonate (BMS-820132)

著者 (63件)： Shi Yan (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Wang Ying (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Meng Wei (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Brigance Robert P. (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Ryono Denis E. (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Bolton Scott (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Zhang Hao (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Chen Sean (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Smirk Rebecca (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Tao Shiwei (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Tino Joseph A. (Cancer Resistance and Neuroscience Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Williams Kristin N. (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Sulsky Richard (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Nielsen Laura (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Ellsworth Bruce (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Wong Michael K. Y. (Department of Discovery Synthesis, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Sun Jung-Hui (Department of Discovery Synthesis, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Leith Leslie W. (Department of Discovery Synthesis, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Sun Dawn (Department of Discovery Synthesis, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Wu Dauh-Rurng (Department of Discovery Synthesis, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Gupta Anuradha (Department of Discovery Synthesis, Small Molecule Drug Discovery, Research & Early Development, Biocon-Bristol Myers Squibb Research & Development Center, India) ,  Rampulla Richard (Department of Discovery Synthesis, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Mathur Arvind (Department of Discovery Synthesis, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Chen Bang-Chi (Department of Discovery Synthesis, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Wang Aiying (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Fuentes-Catanio Helen G. (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Kunselman Lori (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Cap Michael (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Zalaznick Jacob (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Ma Xiaohui (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Liu Heng (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Taylor Joseph R. (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Zebo Rachel (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Jones Beverly (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Kalinowski Stephen (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Swartz Joann (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Staal Ada (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  O’Malley Kevin (Lead Evaluation, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Kopcho Lisa (Lead Evaluation, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Muckelbauer Jodi K. (Molecular Structure & Design, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Krystek Stanley R. Jr. (Molecular Structure & Design, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Spronk Steven A. (Molecular Structure & Design, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Marcinkeviciene Jovita (Lead Evaluation, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Everlof Gerry (Pharmaceutics, Preclinical Candidate Optimization, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Chen Xue-Qing (Pharmaceutics, Preclinical Candidate Optimization, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Xu Carrie (Pharmaceutics, Preclinical Candidate Optimization, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Li Yi-Xin (Pharmaceutics, Preclinical Candidate Optimization, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Langish Robert A. (Pharmaceutics, Preclinical Candidate Optimization, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Yang Yanou (Pharmaceutics, Preclinical Candidate Optimization, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Wang Qi (Pharmaceutics, Preclinical Candidate Optimization, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Behnia Kamelia (Pharmaceutics, Preclinical Candidate Optimization, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Fura Aberra (Pharmaceutics, Preclinical Candidate Optimization, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Janovitz Evan B. (Drug Development and Preclinical Studies, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Pannacciulli Nicola (Clinical Pharmacology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Griffen Steven (Clinical Pharmacology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Zinker Bradley A. (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Krupinski John (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Kirby Mark (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Whaley Jean (Cardiovascular & Fibrosis Discovery Biology, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Zahler Robert (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Barrish Joel C. (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Robl Jeffrey A. (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States) ,  Cheng Peter T. W. (Fibrosis Chemistry, Small Molecule Drug Discovery, Research & Early Development, Bristol Myers Squibb Company, New Jersey, United States)
資料名： Journal of Medicinal Chemistry  (Journal of Medicinal Chemistry)
巻： 65  号： 5  ページ： 4291-4317  発行年： 2022年 
JST資料番号： D0102A  ISSN： 0022-2623  CODEN： JMCMAR  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： アメリカ合衆国 (USA)  言語： 英語 (EN)

抄録/ポイント： グルコキナーゼ(GK)は,グルコースホメオスタシスの重要なレギュレーターであり,その小分子活性化剤は,2型糖尿病の治療に対する有望な機会を提供する。いくつかのGK活性化剤は臨床試験に進歩し,有望な有効性を示した。しかしながら,低血糖は,この機構の重要なリスクを示す。GK機構の有効性を維持しながら,この低血糖リスクを緩和する努力において,著者らは,一連のアミノヘテロアリールホスホン酸ベンズアミドを,ΔΨ部分GK活性化剤として研究した。「部分的GK活性化因子」31(BMS-820132)の発見に culminatedした「完全GK活性化剤」11から出発する構造活性相関研究について論じた。31とその薬物動態(PK)の合成およびin vitroおよびin vivo前臨床薬理学プロファイルを,その有望なin vivo有効性および前臨床ADMEおよび安全性プロファイルに基づいて記述し,31をヒト臨床試験に進めた。Copyright 2022 American Chemical Society All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： *グルコキナーゼ ,  ヒト ,  薬物動力学 ,  臨床試験 ,  低血糖症 ,  有効性 ,  小分子 ,  2型糖尿病 ,  in vitro実験 ,  臨床薬理
準シソーラス用語： 活性化剤 ,  ADME ,  グルコースホメオスタシス ,  構造活性相関研究 , 【Automatic Indexing@JST】

分類 (2件)： 糖質代謝作用薬の基礎研究  (GW13020Q) ,  薬物の構造活性相関  (GV01050B)

タイトルに関連する用語 (9件)： グルコキナーゼ ,  臨床 ,  発見 ,  ジエチル ,  アゼチジン ,  カルボニル ,  ピラジン ,  1H-ピラゾール ,  BMS