5,8-dihydro-5,8-epoxyquinoline | 36178-06-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5,8-dihydro-5,8-epoxyquinoline
• 英文别名: 5,8-dihydro-5,8-epioxido-quinoline；11-Oxa-3-azatricyclo[6.2.1.02,7]undeca-2(7),3,5,9-tetraene
• CAS: 36178-06-0
• 化学式: C₉H₇NO
• 分子量: 145.161
• InChiKey: DNCOFRLRDSGCBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 5,8-dihydro-5,8-epoxyquinoline 在 palladium diacetate 作用下， 以 四氢呋喃 为溶剂， 以65%的产率得到
  参考文献：
  名称：

  环丙烷化 [2.2.1] 杂双环烯烃的合成：改进程序

  摘要：

  摘要 对我们之前关于钯催化杂双环烯烃环丙烷化的报告，开发了一种更安全和改进的方法。通过使用四氢呋喃作为溶剂和更稀的 NaOH 水溶液从重氮甲烷生成重氮甲烷，可以在反应过程中以最小的调整顺利实现环丙烷化。具有庞大 C1 或 C2 基团的 7-氧杂双环底物以及具有各种 N 取代基的 2,3-二氮杂双环底物有效地进行了环丙烷化。使用这种方法，先前报道的产品的产率显着增加，并制备了 10 种新的环丙烷化 [2.2.1] 杂双环产品。此外，这项工作首次报道了 2,3-二氮杂双环烯烃的环丙烷化反应，产率均超过 90%。图形概要

  DOI：

  10.1080/00397911.2015.1118124
• 作为产物：
  描述：

  2-羟基吡啶 在 2,6-二叔丁基-4-甲基吡啶 、 cesium fluoride 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 33.5h， 生成 5,8-dihydro-5,8-epoxyquinoline
  参考文献：
  名称：

  通过氟化物诱导的脱甲硅烷基化消除形成 2,3-吡啶

  摘要：

  摘要 报道了使用无水 CsF 通过脱甲硅烷基化-消除序列形成 2,3-吡啶。

  DOI：

  10.1080/00397919708007079

文献信息

• [EN] CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE<br/>[FR] DÉRIVÉS DE CHROMANE, D'ISOCHROMANE ET DE DIHYDROISOBENZOFURANE EN TANT QUE MODULATEURS ALLOSTÉRIQUES NÉGATIFS DE MGLUR2, COMPOSITIONS ET LEUR UTILISATION
  申请人：MERCK SHARP & DOHME

  公开号：WO2018063955A1

  公开（公告）日：2018-04-05

  The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from (II), (III), (IV), and (V), and ring B, n, R1, R2, R2A, R3, and R3A are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild congnitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

  本发明提供了某些取代的色苷、异色苷和二氢异苯并呋喃化合物的化学结构（I），或其药学上可接受的盐，其中环A是从（II）、（III）、（IV）和（V）中选择的基团，环B、n、R1、R2、R2A、R3和R3A如本文所定义。本发明的化合物可用作mGluR2抑制剂，或mGluR2负向变构调节剂（NAMs），并可用于治疗mGluR2-NAM受体参与的疾病或障碍的方法，如阿尔茨海默病、认知障碍、轻度认知障碍、精神分裂症和其他情绪障碍、疼痛障碍和睡眠障碍，通过向患者投予本发明化合物或其药学上可接受的盐的治疗有效量。本发明还涉及含有本发明化合物或其药学上可接受的盐（可选地与一个或多个额外活性成分组合）和药学上可接受的载体的药物组合物，以及在治疗这些疾病中使用本发明的化合物和药物组合物。
• Chromane, isochromane and dihydroisobenzofuran derivatives as mGluR2—negative allosteric modulators, compositions, and their use
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10335399B2

  公开（公告）日：2019-07-02

  The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from: and ring B, n, R1, R2, R2A, R3, and R3A are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

  本发明提供了某些取代的式 (I) 的铬烷、异铬烷和二氢异苯并呋喃化合物： 或其药学上可接受的盐，其中环 A 是选自以下的分子 和环 B、n、R1、R2、R2A、R3 和 R3A 如本文所定义。本发明的化合物可用作 mGluR2 抑制剂或 mGluR2 负性异位调节剂 (NAM)，并可用于通过向患者施用治疗有效量的本发明化合物或其药学上可接受的盐，来治疗患者涉及 mGluR2-NAM 受体的疾病或紊乱，如阿尔茨海默病、认知障碍、轻度认知障碍、精神分裂症和其他情绪紊乱、疼痛紊乱和睡眠紊乱。本发明还涉及包含本发明化合物或其药学上可接受的盐的药物组合物（可选择与一种或多种其它活性成分组合）和药学上可接受的载体，以及本发明化合物和药物组合物在治疗此类疾病中的用途。
• Chromane, isochromane and dihydroisobenzofuran derivatives as mGluR2-negative allosteric modulators, compositions, and their use
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10806724B2

  公开（公告）日：2020-10-20

  The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from: and ring B, n, R1, R2, R2A, R3, and R3A are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

  本发明提供了某些取代的式 (I) 的铬烷、异铬烷和二氢异苯并呋喃化合物： 或其药学上可接受的盐，其中环 A 是选自以下的分子 和环 B、n、R1、R2、R2A、R3 和 R3A 如本文所定义。本发明的化合物可用作 mGluR2 抑制剂或 mGluR2 负性异位调节剂 (NAM)，并可用于通过向患者施用治疗有效量的本发明化合物或其药学上可接受的盐，来治疗患者涉及 mGluR2-NAM 受体的疾病或紊乱，如阿尔茨海默病、认知障碍、轻度认知障碍、精神分裂症和其他情绪紊乱、疼痛紊乱和睡眠紊乱。本发明还涉及包含本发明化合物或其药学上可接受的盐的药物组合物（可选择与一种或多种其它活性成分组合）和药学上可接受的载体，以及本发明化合物和药物组合物在治疗此类疾病中的用途。
• Rh(I)-Catalyzed Ring-Opening of Hetaryne−Furan Diels−Alder Adducts: Rapid Access to Stereochemically Defined Heterocyclic Scaffolds
  作者：Trung D. Nguyen、Robert Webster、Mark Lautens

  DOI：10.1021/ol200057j

  日期：2011.3.18

  Probing the nucleophilic ring-opening of various bicyclic [2.2.1] hetaryne-furan Diels-Alder adducts revealed that efficient reactivity could be observed with heteroatom nucleophiles by using a cationic Rh(I) complex in combination with a chiral Josiphos-type phosphine ligand. Remarkably, this catalyst system was not impeeded by the incorporation of a heteroatom into the substrate. Racemic materials afforded separable mixtures of enantioenriched regioisomers, indicating that strong reagent control is operative.
• CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3519416A1

  公开（公告）日：2019-08-07