2-氧杂-5-氮杂双环[2.2.2]辛烷半草酸酯 | 1523606-41-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 2-氧杂-5-氮杂双环[2.2.2]辛烷半草酸酯
• 英文名称: 2-oxa-5-azabicyclo[2.2.2]octane hemioxalate
• 英文别名: 2-oxa-5-azabicyclo[2.2.2]octane;oxalic acid
• CAS: 1523606-41-8
• 化学式: C₂H₂O₄*2C₆H₁₁NO
• 分子量: 316.354
• InChiKey: JMGLNUYLNWCZQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.71
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-氧杂-5-氮杂双环[2.2.2]辛烷半草酸酯 、 6-([4-[3-cyano-4-(oxan-4-yloxy)phenyl]pyrimidin-2-yl]amino)-2-methoxypyridine-3-carboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以66%的产率得到5-(2-[[6-methoxy-5-([2-oxa-5-azabicyclo[2.2.2]octan-5-yl]carbonyl)pyridin-2-yl]amino]pyrimidin-4-yl)-2-(oxan-4-yloxy)benzonitrile
  参考文献：
  名称：

  [EN] PYRIMIDINE TBK/IKKε INHIBITOR COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS INHIBITEURS DE PYRIMIDINE TBK/IKKε ET LEURS UTILISATIONS

  摘要：

  这项发明涉及公式I的化合物及其药用可接受的组合物，可用作TBK/IKKε抑制剂。

  公开号：

  WO2019079373A1

文献信息

• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018137593A1

  公开（公告）日：2018-08-02

  Provided are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).

  提供了抑制LRRK2激酶活性的新化合物，以及它们的制备方法、含有它们的组合物以及它们在治疗或预防与LRRK2激酶活性相关或以其为特征的疾病中的用途，例如帕金森病、阿尔茨海默病和肌萎缩侧索硬化症（ALS）。
• [EN] NOVEL TRICYCLIC COMPOUNDS AS INHIBITORS OF MUTANT IDH ENZYMES<br/>[FR] COMPOSÉS TRICYCLIQUES INNOVANTS SERVANT D'INHIBITEURS D'ENZYMES IDH MUTANTES
  申请人：MERCK SHARP & DOHME

  公开号：WO2016089797A1

  公开（公告）日：2016-06-09

  The present invention is directed to tricyclic compounds of formula (I) which are inhibitors of one or more mutant IDH enzymes: (I). The present invention is also directed to uses of the tricyclic compounds described herein in the potential treatment or prevention of cancers in which one or more mutant IDH enzymes are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such cancers.

  本发明涉及式(I)的三环化合物，该化合物是野生型异柠檬酸脱氢酶（IDH）抑制剂：(I)。本发明还涉及将此处描述的三环化合物用于潜在治疗或预防涉及一个或多个突变IDH酶的癌症。本发明还涉及包含这些化合物的组合物。本发明还涉及将这些组合物用于潜在预防或治疗此类癌症。
• [EN] NOVEL TRICYCLIC COMPOUNDS AS INHIBITORS OF MUTANT IDH ENZYMES<br/>[FR] COMPOSÉS TRICYCLIQUES INNOVANTS TELS QUE DES INHIBITEURS D'ENZYMES IDH MUTANTES
  申请人：MERCK SHARP & DOHME

  公开号：WO2017074914A1

  公开（公告）日：2017-05-04

  The present invention is directed to tricyclic compounds of formula (I), (Ia) or (Ib) which are inhibitors of one or more mutant IDH enzymes. The present invention is also directed to uses of these tricyclic compounds in the potential treatment or prevention of cancers in which one or more mutant IDH enzymes are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such cancers.

  本发明涉及式(I)、(Ia)或(Ib)的三环化合物，这些化合物是一种或多种突变的IDH酶的抑制剂。本发明还涉及这些三环化合物在潜在治疗或预防涉及一种或多种突变IDH酶的癌症中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗此类癌症中的用途。
• Diminishing GSH-Adduct Formation of Tricyclic Diazepine-based Mutant IDH1 Inhibitors
  作者：Chunhui Huang、Christian Fischer、Michelle R. Machacek、Stephane Bogen、Tesfaye Biftu、Xianhai Huang、Michael H. Reutershan、Ryan Otte、Qingmei Hong、Zhicai Wu、Yang Yu、Min Park、Lei Chen、Purakkattle Biju、Ian Knemeyer、Ping Lu、Christopher J. Kochansky、Michael Brendan Hicks、Yong Liu、Roy Helmy、Xavier Fradera、Anthony Donofrio、Josh Close、Matthew L. Maddess、Catherine White、David L. Sloman、Nunzio Sciammetta、Jun Lu、Craig Gibeau、Vladimir Simov、Hongjun Zhang、Peter Fuller、David Witter

  DOI：10.1021/acsmedchemlett.2c00089

  日期：2022.4.14

  and III gliomas and ∼10% of acute myeloid leukemia (AML) harbor somatic IDH1 mutations. These mutations confer a neomorphic gain of function, leading to the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG). We identified and developed a potent, selective, and orally bioavailable brain-penetrant tricyclic diazepine scaffold that inhibits mutant IDH1. During the course of in vitro metabolism

  突变异柠檬酸脱氢酶 1 (IDH1) 已被确定为一个有吸引力的肿瘤学靶点，>70% 的 II 级和 III 级神经胶质瘤和约 10% 的急性髓性白血病 (AML) 具有体细胞 IDH1 突变。这些突变赋予新形态的功能获得，导致癌代谢物 ( R )-2-羟基戊二酸 (2-HG) 的产生。我们发现并开发了一种有效的、选择性的和口服生物可利用的脑渗透剂三环二氮卓类支架，可抑制突变体 IDH1。在体外过程中代谢研究中，观察到谷胱甘肽加合物代谢物。GSH 加合物形成的假设是由三环核心的富电子性质驱动的。在此，我们描述了我们为减少核心的富电子性质所做的努力。最终，专注于核心修饰以阻断代谢热点并结合取代模式变化（C8 N → C 连接）的策略导致鉴定出新的三环类似物，其跨物种的 GSH 加合物形成最少，同时保持整体平衡。
• AROMATIC HETEROCYCLIC COMPOUND, PHARMACEUTICAL COMPOSITION AND USE THEREOF
  申请人：GT Apeiron Therapeutics Limited

  公开号：EP4269402A1

  公开（公告）日：2023-11-01

  An aromatic heterocyclic compound, a pharmaceutical composition and use thereof. Specifically disclosed are a compound as shown in formula I, a stereoisomer thereof, a diastereomer thereof, or a pharmaceutically acceptable salt of any one of the foregoing, or a crystal form or solvate of any one of the foregoing. The aromatic heterocyclic compound has a novel structure, good CDK7 inhibitory activity, and good selectivity.

  一种芳香杂环化合物、一种药物组合物及其用途。具体公开了一种如式 I 所示的化合物、其立体异构体、非对映异构体、或前述任一项的药学上可接受的盐，或前述任一项的晶型或溶质。该芳香杂环化合物具有新颖的结构、良好的 CDK7 抑制活性和选择性。