5-bromo-3-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine | 1214900-93-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 5-bromo-3-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine
• 英文别名: 5-Bromo-3-methyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazolo[3,4-b]pyridine；2-[(5-bromo-3-methylpyrazolo[3,4-b]pyridin-1-yl)methoxy]ethyl-trimethylsilane
• CAS: 1214900-93-2
• 化学式: C₁₃H₂₀BrN₃OSi
• 分子量: 342.311
• InChiKey: JNATVLCRBSSZRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.81
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromo-3-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine 在 四羟基二硼 、 2nd Gen. precatalyst cataCXium® 、 双氧水 、 potassium carbonate 、 ammonium bicarbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 5-(2,6-dichloro-4-nitrophenoxy)-3-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine
  参考文献：
  名称：

  WO2021041237A5

  摘要：

  公开号：

  WO2021041237A5
• 作为产物：
  描述：

  5-溴-1H-吡唑[3,4-B]吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium phosphate 、 sodium hydride 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 5-bromo-3-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine
  参考文献：
  名称：

  Identification of GZD824 as an Orally Bioavailable Inhibitor That Targets Phosphorylated and Nonphosphorylated Breakpoint Cluster Region–Abelson (Bcr-Abl) Kinase and Overcomes Clinically Acquired Mutation-Induced Resistance against Imatinib

  摘要：

  Bcr-Abl(T315)I mutation-induced imatinib resistance remains a major challenge for clinical management of chronic myelogenous leukemia (CML). Herein, we report GZD824 (10a) as a novel orally bioavailable inhibitor against a broad spectrum of Bcr-Abl mutants including T315I. It tightly bound to Bcr-Abl(WT) and Bcr-Abl(T315I) with K-d values of 0.32 and 0.71 nM, respectively, and strongly inhibited the kinase functions with nanomolar IC50 values. The compound potently suppressed proliferation of Bcr-Abl-positive K562 and Ku812 human CML cells with IC50 values of 0.2 and 0.13 nM, respectively. It also displayed good oral bioavailability (48.7%), a reasonable half-life (10.6 h), and promising in vivo antitumor efficacy. It induced tumor regression in mouse xenograft tumor models driven by Bcr-Abl(WT) or the mutants and significantly improved the survival of mice bearing an allograft leukemia model with Ba/F3 cells harboring Bcr-Abl(T315I). GZD824 represents a promising lead candidate for development of Bcr-Abl inhibitors to overcome acquired imatinib resistance.

  DOI：

  10.1021/jm301581y

文献信息

• [EN] HETEROCYCLIC KINASE INHIBITORS AND PRODUCTS AND USES THEREOF<br/>[FR] INHIBITEURS DE KINASE HÉTÉROCYCLIQUES, PRODUITS ET UTILISATIONS ASSOCIÉS
  申请人：GB002 INC

  公开号：WO2020264420A1

  公开（公告）日：2020-12-30

  Compounds are provided having the structure of Formula (I) or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, tautomer, isotope, or salt thereof, wherein A, X, R3, R5, R6, R7, R8, Y2, Y4, Y6, Y7, Y8, Y9, m, and n are as defined herein. Such compounds inhibit tyrosine kinase receptors, particularly the platelet derived growth factor receptor - alpha (PDGFR-α) and/or the platelet derived growth factor receptor - beta (PDGFR-β). Products containing such compounds, as well as methods for their use and preparation, are also provided.

  提供具有Formula (I)结构或其药学上可接受的异构体、消旋体、水合物、溶剂合物、互变异构体、同位素或盐的化合物，其中A、X、R3、R5、R6、R7、R8、Y2、Y4、Y6、Y7、Y8、Y9、m和n如本文所定义。这些化合物抑制酪氨酸激酶受体，特别是血小板源性生长因子受体-α（PDGFR-α）和/或血小板源性生长因子受体-β（PDGFR-β）。还提供含有这些化合物的产品，以及其使用和制备方法。
• [EN] METHODS AND COMPOUNDS FOR RESTORING MUTANT P53 FUNCTION<br/>[FR] MÉTHODES ET COMPOSÉS POUR LA RESTAURATION D'UNE FONCTION DE MUTANTS DE P53
  申请人：PMV PHARMACEUTICALS INC

  公开号：WO2021262596A1

  公开（公告）日：2021-12-30

  Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods that restore DNA binding affinity of p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

  癌基因和肿瘤抑制基因的突变促进了癌症的发展和进展。本公开描述了一种恢复p53突变体DNA结合亲和力的化合物和方法。本公开的化合物可以结合突变的p53，并恢复p53突变体结合DNA和激活与肿瘤抑制有关的下游效应子的能力。公开的化合物可用于减少含有p53突变的癌症的进展。
• AMINOTRIAZOLOPYRIDINES, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
  申请人：Bahmanyar Sogole

  公开号：US20100093698A1

  公开（公告）日：2010-04-15

  Provided herein are Heteroaryl Compounds of formula (I): wherein R 1 and R 2 are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing inflammatory conditions or cancer, and conditions treatable or preventable by inhibition of a kinase or a kinase pathway comprising administering an effective amount of a Heteroaryl Compound to a subject in need thereof.

  本文提供了式(I)的杂环芳基化合物：其中R1和R2如本文所定义，包括有效量的杂环芳基化合物的组合物以及治疗或预防炎症性疾病或癌症的方法，以及通过向需要治疗的对象施用有效量的杂环芳基化合物来抑制激酶或激酶途径治疗或预防的疾病。
• Aminotriazolopyridines, compositions thereof, and methods of treatment therewith
  申请人：Signal Pharmaceuticals, LLC

  公开号：US08299056B2

  公开（公告）日：2012-10-30

  Provided herein are Heteroaryl Compounds of formula (I): wherein R1 and R2 are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing inflammatory conditions or cancer, and conditions treatable or preventable by inhibition of a kinase or a kinase pathway comprising administering an effective amount of a Heteroaryl Compound to a subject in need thereof.

  本文提供了式(I)的杂环芳基化合物，其中R1和R2的定义如本文所述，包括含有效量的杂环芳基化合物的组合物以及用于治疗或预防炎症性疾病或癌症，以及通过抑制激酶或激酶途径治疗或预防的疾病，包括向需要治疗的受试者施用有效量的杂环芳基化合物的方法。
• [EN] 6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS<br/>[FR] 6-HÉTÉROARYLOXY BENZIMIDAZOLES ET AZABENZIMIDAZOLES UTILISÉS EN TANT QU'INHIBITEURS DE JAK2
  申请人：AJAX THERAPEUTICS INC

  公开号：WO2022140527A1

  公开（公告）日：2022-06-30

  The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.

  本公开提供6-杂环氧基苯并咪唑和氮杂苯并咪唑化合物及其组合物，用于抑制JAK2。