1-甲基-3-溴-4-氨基吡唑[3,4-d]并嘧啶 | 83255-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 1-甲基-3-溴-4-氨基吡唑[3,4-d]并嘧啶
• 英文名称: 3-bromo-1-methyl-4-aminopyrazolo<3,4-d>pyrimidine
• 英文别名: 3-bromo-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine；3-bromo-1-methylpyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 83255-87-2
• 化学式: C₆H₆BrN₅
• mdl: MFCD22375270
• 分子量: 228.051
• InChiKey: DHFYKLULHRGVSL-UHFFFAOYSA-N

物化性质

• 熔点：
  221-223 °C(Solv: ethanol (64-17-5))
• 沸点：
  410.4±40.0 °C(Predicted)
• 密度：
  2.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-甲基-3-溴-4-氨基吡唑[3,4-d]并嘧啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N-(4-(4-amino-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl)-5-(4-fluorophenyl)-1-(tetrahydrofuran-3-ylmethyl)-4-oxo-1,4-dihydropyridazine-3-carboxamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUND AND PREPARATION METHOD THEREFOR AND USE THEREOF
  [FR] COMPOSÉ HÉTÉROCYCLIQUE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION
  [ZH] 一类杂环化合物及其制备方法和用途

  摘要：

  本发明涉及一类杂环化合物及其制备方法和用途。具体而言，本发明涉及式I的化合物或其药学上可接受的盐、立体异构体、互变异构体、多晶型物、溶剂合物、N-氧化物、同位素标记的化合物、代谢物或前药，包含其的药物组合物和药盒，其制备方法及其在制备用于预防或治疗与Axl和/或Mer相关的疾病(特别是肿瘤疾病)的药物中的用途。

  公开号：

  WO2023016296A1
• 作为产物：
  描述：

  1-甲基-4-氨基-1H-吡唑并[3,4-D]嘧啶 在 溴 作用下， 以 水 为溶剂， 以55%的产率得到1-甲基-3-溴-4-氨基吡唑[3,4-d]并嘧啶
  参考文献：
  名称：

  4-氨基吡唑并[3,4-d]嘧啶的一些反应

  摘要：

  DOI：

  10.1007/bf00568958

文献信息

• [EN] TRIAZOLONE COMPOUNDS AS PERK INHIBITORS<br/>[FR] COMPOSÉS DE TRIAZOLONE COMME INHIBITEURS DE PERK
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO 2) LTD

  公开号：WO2017046738A1

  公开（公告）日：2017-03-23

  The invention is directed to substituted triazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, X, Y, Y1, and Z are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-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, 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.

  这项发明涉及取代三唑烷酮衍生物。具体而言，该发明涉及符合以下式(I)的化合物：其中R1、R2、R3、R4、R5、X、Y、Y1和Z如本文所定义。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、阿尔茨海默病、神经病痛、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、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-皮克氏病、淀粉样变性、认知障碍、动脉粥样硬化、眼部疾病、心律失常、器官移植以及器官移植用途中的运输。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该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。
• [EN] HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES À UTILISER EN TANT QU'INHIBITEURS DE KINASES RET
  申请人：CANCER RES TECH LTD

  公开号：WO2017178845A1

  公开（公告）日：2017-10-19

  The present invention relates to compounds of formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, X1, X2, X3, X4, integer a and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.

  本发明涉及作为RET（重排基因转位）激酶酶活性抑制剂的I式化合物：其中HET、X1、X2、X3、X4、整数a和R3各自如本文所定义。本发明还涉及制备这些化合物的方法，包括它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及其他涉及RET激酶活性的疾病或病况中的用途。
• KINASE INHIBITORS
  申请人：PRINCIPIA BIOPHARMA, INC.

  公开号：US20140323464A1

  公开（公告）日：2014-10-30

  Provided herein are kinase inhibiting compounds and methods of using the same.

  提供的是激酶抑制化合物及其使用方法。
• [EN] HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE KINASE RET
  申请人：CANCER RES TECH LTD

  公开号：WO2017178844A1

  公开（公告）日：2017-10-19

  The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X1, X2, X3, X4, R2, and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.

  本发明涉及具有以下结构的Formula I化合物，其作为RET（重排基因转座）激酶酶活性的抑制剂：其中HET，键a、b、c和d，X1、X2、X3、X4、R2和R3在此处各自定义。本发明还涉及制备这些化合物的方法，包括它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及其他涉及RET激酶活性的疾病或症状中的用途。
• [EN] CHEMICAL COMPOUNDS ACTING AS PERK INHIBITORS<br/>[FR] COMPOSÉS CHIMIQUES AGISSANT COMME INHIBITEURS DE PERK
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2015136463A1

  公开（公告）日：2015-09-17

  The invention is directed to substituted pyrrolidinone derivatives. Specifically, the invention is directed to compounds according to Formula X: wherein R41, R42, R43, R44, R45, R46, and R47 are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt- Jakob Disease, and related prion diseases, amyotrophic lateral sclerosis, myocardial infarction, neurodegeneration, cardiovascular disease, atherosclerosis, ocular diseases, and arrhythmias, more specifically cancers of the breast, colon, pancreas 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.

  该发明涉及取代吡咯烷酮衍生物。具体而言，该发明涉及符合以下X式的化合物：其中R41、R42、R43、R44、R45、R46和R47在此处被定义。该发明的化合物是PERK的抑制剂，可用于治疗癌症以及与激活的未折叠蛋白质反应途径相关的疾病，如阿尔茨海默病、中风、糖尿病、帕金森病、亨廷顿病、克雅茨菲尔德-雅各布病和相关朊蛋白病、肌萎缩侧索硬化、心肌梗死、神经退行性疾病、心血管疾病、动脉粥样硬化、眼部疾病和心律失常，更具体地包括乳腺、结肠、胰腺和肺癌。因此，该发明还涉及包含该发明的化合物的药物组合物。该发明还进一步涉及使用该发明的化合物或包含该发明的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。