1-(1-acetyl-2,3-dihydro-1H-indol-5-yl)-2-bromoethanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-(1-acetyl-2,3-dihydro-1H-indol-5-yl)-2-bromoethanone
• 英文别名: 1-Acetyl-5-(bromoacetyl)indoline；1-(1-acetylindolin-5-yl)-2-bromo-ethanone；1-(1-acetyl-2,3-dihydro-1H-indol-5-yI)-2-bromoethanone；1-(1-acetyl-2,3-dihydroindol-5-yl)-2-bromoethanone
• 化学式: C₁₂H₁₂BrNO₂
• 分子量: 282.137
• InChiKey: SXDJJQWHXHEGKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(1-acetyl-2,3-dihydro-1H-indol-5-yl)-2-bromoethanone 在 氨 、 sodium acetate 、 二乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.88h， 生成 5-(1-acetyl-2,3-dihydro-1H-indol-5-yl)furo[2,3-d]pyrimidin-4-amine
  参考文献：
  名称：

  [EN] CHEMICAL COMPOUNDS
  [FR] COMPOSÉS CHIMIQUES

  摘要：

  公开号：

  WO2011119663A8
• 作为产物：
  描述：

  1,5-二乙酰基二氢吲哚 在 pyridinium hydrobromide perbromide 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以93%的产率得到1-(1-acetyl-2,3-dihydro-1H-indol-5-yl)-2-bromoethanone
  参考文献：
  名称：

  Discovery of 7-Methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a Potent and Selective First-in-Class Inhibitor of Protein Kinase R (PKR)-like Endoplasmic Reticulum Kinase (PERK)

  摘要：

  Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is activated in response to a variety of endoplasmic reticulum stresses implicated in numerous disease states. Evidence that PERK is implicated in tumorigenesis and cancer cell survival stimulated our search for small molecule inhibitors. Through screening and lead optimization using the human PERK crystal structure, we discovered compound 38 (GSK2606414), an orally available, potent, and selective PERK inhibitor. Compound 38 inhibits PERK activation in cells and inhibits the growth of a human tumor xenograft in mice.

  DOI：

  10.1021/jm300713s

文献信息

• 2-CARBOXAMIDE-7-PIPERAZINYL-BENZOFURAN DERIVATIVES 774
  申请人：ANDERSSON Johan

  公开号：US20100331341A1

  公开（公告）日：2010-12-30

  The present invention relates to compounds of formula (I), wherein R 1 is heteroaryl or heterocyclyl, optionally substituted; R 2 is C 1-4 alkyl, heterocyclyl, C 1-4 alkylaryl, C 1-4 alkylheteroaryl, carbocyclyl, C 1-4 alkylheterocyclyl, heterocyclyl-heteroaryl, aryl-heterocyclyl, carbocyclyl-heteroaryl, heterocyclyl-aryl, optionally substituted; R 3 is hydrogen or C 1-4 alkyl, or R 2 and R 3 may together with the nitrogen atom, form a saturated ring system containing 4, 5 or 6 ring forming atoms, and optionally substituted; R 4 is hydrogen, halogen, methyl or methoxy; to pharmaceutical composition containing said compounds and to the use of said compounds in therapy, for instance in treating cognitive disorders. The present invention further relates to new intermediates useful in the preparation thereof.

  本发明涉及公式（I）的化合物，其中R1是杂环芳基或杂环烷基，可选择性取代；R2是C1-4烷基，杂环烷基，C1-4烷基芳基，C1-4烷基杂环芳基，碳环烷基，C1-4烷基杂环烷基，杂环烷基-杂环芳基，芳基-杂环烷基，碳环烷基-杂环芳基，杂环烷基-芳基，可选择性取代；R3是氢或C1-4烷基，或R2和R3可以与氮原子一起形成含有4、5或6个环形成原子的饱和环系统，并可选择性取代；R4是氢，卤素，甲基或甲氧基；含有所述化合物的药物组合物以及所述化合物在治疗中的使用，例如用于治疗认知障碍。本发明还涉及制备中间体的新方法。
• CHEMICAL COMPOUNDS
  申请人：Axten Jeffrey Michael

  公开号：US20120077828A1

  公开（公告）日：2012-03-29

  The invention is directed to substituted indoline derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R 1 , R 2 , and R 3 are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, ocular diseases, and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, Type 1 diabetes Parkinson disease, Huntington's disease, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, atherosclerosis, and arrhythmias, and more specifically cancers of the breast, colon, pancreatic, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代的吲哚啉衍生物。具体而言，本发明涉及按式I所示的化合物：其中R1、R2和R3在此定义。本发明的化合物是PERK的抑制剂，可用于治疗癌症、眼部疾病和与激活的未折叠蛋白质应答途径相关的疾病，如阿尔茨海默病、中风、1型糖尿病帕金森病、亨廷顿病、肌萎缩性侧索硬化、心肌梗死、心血管疾病、动脉硬化和心律失常，更具体地，乳腺癌、结肠癌、胰腺癌和肺癌。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还涉及使用本发明化合物或包含本发明化合物的药物组合物抑制PERK活性和治疗相关疾病的方法。
• 2-carboxamide-7-piperazinyl-benzofuran derivatives 774
  申请人：Andersson Johan

  公开号：US08367676B2

  公开（公告）日：2013-02-05

  The present invention relates to compounds of formula (I), wherein R1 is heteroaryl or heterocyclyl, optionally substituted; R2 is C1-4alkyl, heterocyclyl, C1-4alkylaryl, C1-4alkylheteroaryl, carbocyclyl, C1-4alkylheterocyclyl, heterocyclyl-heteroaryl, aryl-heterocyclyl, carbocyclyl-heteroaryl, heterocyclyl-aryl, optionally substituted; R3 is hydrogen or C1-4alkyl, or R2 and R3 may together with the nitrogen atom, form a saturated ring system containing 4, 5 or 6 ring forming atoms, and optionally substituted; R4 is hydrogen, halogen, methyl or methoxy; to pharmaceutical composition containing said compounds and to the use of said compounds in therapy, for instance in treating cognitive disorders. The present invention further relates to new intermediates useful in the preparation thereof.

  本发明涉及式（I）的化合物，其中R1为杂环芳基或杂环烷基，可选地取代；R2为C1-4烷基，杂环基，C1-4烷基芳基，C1-4烷基杂环芳基，碳环基，C1-4烷基杂环基，杂环基-杂环芳基，芳基-杂环基，碳环基-杂环芳基，杂环基-芳基，可选地取代；R3为氢或C1-4烷基，或R2和R3可以与氮原子一起形成含有4、5或6个环形成原子的饱和环系统，可选地取代；R4为氢、卤素、甲基或甲氧基；含有上述化合物的制药组合物以及上述化合物在治疗中的用途，例如治疗认知障碍。本发明还涉及在制备中有用的新中间体。
• 2-carboxamide-7-piperazinyl-benzofuran derivatives
  申请人：AstraZeneca AB

  公开号：US08859534B2

  公开（公告）日：2014-10-14

  The present invention relates to compounds of formula (I), wherein R1 is heteroaryl or heterocyclyl, optionally substituted; R2 is C1-4alkyl, heterocyclyl, C1-4alkylaryl, C1-4alkylheteroaryl, carbocyclyl, C1-4alkylheterocyclyl, heterocyclyl-heteroaryl, aryl-heterocyclyl, carbocyclyl-heteroaryl, heterocyclyl-aryl, optionally substituted; R3 is hydrogen or C1-4alkyl, or R2 and R3 may together with the nitrogen atom, form a saturated ring system containing 4, 5 or 6 ring forming atoms, and optionally substituted; R4 is hydrogen, halogen, methyl or methoxy; to pharmaceutical composition containing said compounds and to the use of said compounds in therapy, for instance in treating cognitive disorders. The present invention further relates to new intermediates useful in the preparation thereof.

  本发明涉及公式（I）的化合物，其中R1是杂环芳基或杂环烷基，可选择性取代；R2是C1-4烷基，杂环基，C1-4烷基芳基，C1-4烷基杂环芳基，碳环基，C1-4烷基杂环基，杂环基-杂环芳基，芳基-杂环基，碳环基-杂环芳基，杂环基-芳基，可选择性取代；R3是氢或C1-4烷基，或R2和R3可以与氮原子一起形成含有4、5或6个环形成原子的饱和环系统，可选择性取代；R4是氢、卤素、甲基或甲氧基；以及含有该化合物的制药组合物以及该化合物在治疗中的使用，例如用于治疗认知障碍。本发明还涉及在其制备中有用的新中间体。
• 2-Carboxamide-7-Piperazinyl-Benzofuran Derivatives
  申请人：ASTRAZENECA AB

  公开号：US20130296296A1

  公开（公告）日：2013-11-07

  The present invention relates to compounds of formula (I), wherein R 1 is heteroaryl or heterocyclyl, optionally substituted; R 2 is C 1-4 alkyl, heterocyclyl, C 1-4 alkylaryl, C 1-4 alkylheteroaryl, carbocyclyl, C 1-4 alkylheterocyclyl, heterocyclyl-heteroaryl, aryl-heterocyclyl, carbocyclyl-heteroaryl, heterocyclyl-aryl, optionally substituted; R 3 is hydrogen or C 1-4 alkyl, or R 2 and R 3 may together with the nitrogen atom, form a saturated ring system containing 4, 5 or 6 ring forming atoms, and optionally substituted; R 4 is hydrogen, halogen, methyl or methoxy; to pharmaceutical composition containing said compounds and to the use of said compounds in therapy, for instance in treating cognitive disorders. The present invention further relates to new intermediates useful in the preparation thereof.

  本发明涉及式（I）的化合物，其中R1是杂环芳基或杂环基，可选地被取代；R2是C1-4烷基，杂环基，C1-4烷基芳基，C1-4烷基杂环芳基，碳环基，C1-4烷基杂环基，杂环基-杂环芳基，芳基-杂环基，碳环基-杂环芳基，杂环基-芳基，可选地被取代；R3是氢或C1-4烷基，或R2和R3可以与氮原子一起形成4、5或6个环形成原子的饱和环系统，可选地被取代；R4是氢、卤素、甲基或甲氧基；以及含有所述化合物的制药组合物和所述化合物在治疗中的用途，例如用于治疗认知障碍。本发明还涉及在其制备中有用的新中间体。