5-bromo-4-fluoro-3-methyl-1H-indazole | 1360945-67-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 5-bromo-4-fluoro-3-methyl-1H-indazole
• 英文别名: 5-bromo-4-fluoro-3-methyl-2H-indazole
• CAS: 1360945-67-0
• 化学式: C₈H₆BrFN₂
• 分子量: 229.051
• InChiKey: DESNPJVSMWSJOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-4-fluoro-3-methyl-1H-indazole 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 copper diacetate 吡啶 、 氧气 、 sodium acetate 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0~80.0 ℃ 、413.7 kPa 条件下， 反应 120.0h， 生成 methyl 1-(5-chloro-6-cyclopropylpyridin-3-yl)-4-fluoro-3-methyl-1H-indazole-5-carboxylate
  参考文献：
  名称：

  [EN] INDAZOLE DERIVATIVES AS SODIUM CHANNEL INHIBITORS
  [FR] DÉRIVÉS D'INDAZOLE COMME INHIBITEURS DES CANAUX SODIQUES

  摘要：

  该发明涉及酰基磺酰胺衍生物，其在医学上的应用，含有它们的组合物，其制备方法以及在这些方法中使用的中间体。更具体地，该发明涉及一种新的酰基磺酰胺Nav1.7抑制剂，其化学式为(I)：或其药用可接受盐，其中U、V、W、X、Y、R°和R1如描述中定义。Nav 1.7抑制剂在治疗各种疾病，特别是疼痛方面具有潜在用途。

  公开号：

  WO2012095781A1
• 作为产物：
  描述：

  1-(3-bromo-2,6-difluorophenyl)ethanone 在 一水合肼 作用下， 以 乙二醇二甲醚 为溶剂， 反应 12.0h， 以12.5%的产率得到5-bromo-4-fluoro-3-methyl-1H-indazole
  参考文献：
  名称：

  [EN] INHIBITORS OF ENL/AF9 YEATS
  [FR] INHIBITEURS DE YEATS ENL/AF9

  摘要：

  揭示了用于治疗白血病的方法和组合物。以下式的酰化6-氨基吲哚，酰化6-氨基吡咯吡啶和酰化3-氨基吡咯并[3,2-c]吡啉酮抑制ENL/AF9 YEATS，因此对治疗白血病有用。

  公开号：

  WO2021127166A1

文献信息

• [EN] INDAZOLE DERIVATIVES USEFUL AS PERK INHIBITORS<br/>[FR] DÉRIVÉS D'INDAZOLE UTILES EN TANT QU'INHIBITEURS DE PERK
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2019021208A1

  公开（公告）日：2019-01-31

  The invention is directed to substituted indazole derivatives and uses thereof. Specifically, the invention is directed to compounds according to Formula I and the use of compounds of Formula (I) in treating disease states (I) wherein R1, R2, R3, R4, R5, are as defined herein; or a salt thereof including a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, fatal familial insomnia, Gerstmann-Straussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, neurological disorders, pain, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. 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.

  这项发明涉及取代吲唑衍生物及其用途。具体而言，该发明涉及符合式I的化合物以及在治疗疾病状态中使用符合式(I)的化合物，其中R1、R2、R3、R4、R5如本文所定义；或其盐，包括其药用可接受盐。该发明的化合物是PERK的抑制剂，可用于治疗癌症、癌前综合征以及与激活的未折叠蛋白反应途径相关的疾病，如阿尔茨海默病、脊髓损伤、创伤性脑损伤、缺血性中风、中风、帕金森病、糖尿病、代谢综合征、代谢紊乱、亨廷顿病、克雅氏病、及相关朊蛋白病、致命性家族性失眠、格斯特曼-施特劳斯勒-谢因克症候群、及相关朊蛋白病、肌萎缩侧索硬化、进行性核上性麻痹、心肌梗死、心血管疾病、炎症、器官纤维化、肝脏慢性和急性疾病、脂肪肝病、肝脂肪变性、肝纤维化、肺部慢性和急性疾病、肺纤维化、肾脏慢性和急性疾病、肾脏纤维化、慢性创伤性脑病（CTE）、神经退行性疾病、痴呆症、额颞叶痴呆症、tau蛋白病、皮克氏病、尼曼-匹克氏病、淀粉样变性、认知障碍、动脉粥样硬化、眼部疾病、神经系统疾病、疼痛、心律失常、器官移植以及器官移植用途。因此，该发明进一步涉及包括该发明化合物的药物组合物。该发明还进一步涉及通过使用该发明的化合物或包括该发明化合物的药物组合物来抑制PERK活性和治疗相关疾病的方法。
• [EN] HETEROCYCLIC COMPOUND<br/>[FR] COMPOSÉ HÉTÉROCYCLIQUE
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2015005489A1

  公开（公告）日：2015-01-15

  Provided is a compound having a melanin-concentrating hormone receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of obesity and the like. A compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  提供的是一种具有黑色素浓缩激素受体拮抗作用的化合物，可用作预防或治疗肥胖等疾病的药物。该化合物由以下式（I）表示：其中每个符号如规范中定义，或其盐。
• 2,4-DISUBSTITUTED PYRIMIDINE DERIVATIVE AS CDK INHIBITOR AND USE THEREOF
  申请人：Shanghai Xunhe Pharmaceutical Technology Co., Ltd.

  公开号：EP3444246A1

  公开（公告）日：2019-02-20

  The present invention relates to a 2,4-disubstituted pyrimidine derivative and the use thereof as a therapeutically effective cyclin-dependent kinase(CDK) inhibitor. In particular, the present invention relates to the use of a new 2,4-disubstituted pyrimidine derivativeas shown in formula (I) and a pharmaceutical composition thereof as a selective CDK4/6inhibitor in preventing or treating diseases related to CDK4/6.

  本发明涉及一种2,4-二取代嘧啶衍生物及其作为治疗有效的细胞周期蛋白依赖性激酶（CDK）抑制剂的用途。特别是，本发明涉及一种如式（I）所示的新型 2,4-二取代嘧啶衍生物及其药物组合物作为选择性 CDK4/6 抑制剂在预防或治疗与 CDK4/6 有关的疾病中的用途。
• 2,4-disubstituted pyrimidines as CDK inhibitors
  申请人：Shanghai Xunhe Pharmaceutical Technology Co. Ltd.

  公开号：US10464927B2

  公开（公告）日：2019-11-05

  The present disclosure relates to a 2,4-disubstituted pyrimidine derivative and the use thereof as a therapeutically effective cyclin-dependent kinase (CDK) inhibitor. In particular, the present disclosure relates to the use of a new 2,4-disubstituted pyrimidine derivatives shown in formula (I) and a pharmaceutical composition thereof as a selective CDK4/6 inhibitor in preventing or treating diseases related to CDK4/6.

  本公开涉及一种2,4-二取代嘧啶衍生物及其作为治疗有效的细胞周期蛋白依赖性激酶（CDK）抑制剂的用途。特别是，本公开涉及式（I）所示的一种新的2,4-二取代嘧啶衍生物及其药物组合物作为选择性CDK4/6抑制剂在预防或治疗与CDK4/6有关的疾病中的用途。
• 2,4-Disubstituted Pyrimidine Derivative as CDK Inhibitor and Use Thereof
  申请人：Shanghai Xunhe Pharmaceutical Technology Co. Ltd.

  公开号：US20190071427A1

  公开（公告）日：2019-03-07

  The present disclosure relates to a 2,4-disubstituted pyrimidine derivative and the use thereof as a therapeutically effective cyclin-dependent kinase (CDK) inhibitor. In particular, the present disclosure relates to the use of a new 2,4-disubstituted pyrimidine derivatives shown in formula (I) and a pharmaceutical composition thereof as a selective CDK4/6 inhibitor in preventing or treating diseases related to CDK4/6.