tert-butyl ((5-bromo-4-methylpyridin-3-yl)methyl)(ethyl)carbamate | 351458-27-0

• 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: tert-butyl ((5-bromo-4-methylpyridin-3-yl)methyl)(ethyl)carbamate
• 英文别名: (5-bromo-4-methyl-pyridin-3-ylmethyl)-ethyl-carbamic acid tert-butyl ester；Tert-butyl (5-bromo-4-methylpyridin-3-yl)methyl(ethyl)carbamate；tert-butyl N-[(5-bromo-4-methylpyridin-3-yl)methyl]-N-ethylcarbamate
• CAS: 351458-27-0
• 化学式: C₁₄H₂₁BrN₂O₂
• 分子量: 329.237
• InChiKey: RVYBPFCJSFEEIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl ((5-bromo-4-methylpyridin-3-yl)methyl)(ethyl)carbamate 在 三乙基硅烷 、 sodium hydrogen sulfate 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N,N-二甲基乙酰胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 35.0h， 生成 N-((5-(4-(3-(4,6-difluoro-1H-benzo[d]imidazol-2-yl)-1H-pyrazol-4-yl)phenyl)-4-methylpyridin-3-yl)methyl)ethanamine
  参考文献：
  名称：

  通过生成模型和基于结构的药物设计加速发现大环 CDK2 抑制剂 QR-6401

  摘要：

  选择性 CDK2 抑制剂有潜力为 CDK2 依赖性癌症提供有效的治疗，并对抗由于细胞周期蛋白 E1 (CCNE1) 固有高表达或 CDK4/6 抑制剂治疗诱导的 CCNE1 扩增而产生的耐药性。利用深度学习的生成模型越来越多地集成到早期药物发现中，以实现命中识别和先导化合物优化。在这里，我们报告了一种高效、选择性大环 CDK2 抑制剂 QR-6401 ( 23 ) 的发现，该发现通过应用生成模型和基于结构的药物设计 (SBDD) 加速。 QR-6401 ( 23 ) 通过口服给药在 OVCAR3 卵巢癌异种移植模型中表现出强大的抗肿瘤功效。

  DOI：

  10.1021/acsmedchemlett.2c00515
• 作为产物：
  描述：

  3,5-二溴-4-甲基吡啶 在 正丁基锂 、 乙胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 33.92h， 生成 tert-butyl ((5-bromo-4-methylpyridin-3-yl)methyl)(ethyl)carbamate
  参考文献：
  名称：

  通过生成模型和基于结构的药物设计加速发现大环 CDK2 抑制剂 QR-6401

  摘要：

  选择性 CDK2 抑制剂有潜力为 CDK2 依赖性癌症提供有效的治疗，并对抗由于细胞周期蛋白 E1 (CCNE1) 固有高表达或 CDK4/6 抑制剂治疗诱导的 CCNE1 扩增而产生的耐药性。利用深度学习的生成模型越来越多地集成到早期药物发现中，以实现命中识别和先导化合物优化。在这里，我们报告了一种高效、选择性大环 CDK2 抑制剂 QR-6401 ( 23 ) 的发现，该发现通过应用生成模型和基于结构的药物设计 (SBDD) 加速。 QR-6401 ( 23 ) 通过口服给药在 OVCAR3 卵巢癌异种移植模型中表现出强大的抗肿瘤功效。

  DOI：

  10.1021/acsmedchemlett.2c00515

文献信息

• 3,5 Disubstituted indazole compounds with nitrogen-bearing 5-membered heterocycles, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation
  申请人：McAlpine James Indrawan

  公开号：US20050090529A1

  公开（公告）日：2005-04-28

  3,5 disubstituted indazole compounds with substituted nitrogen bearing 5-membered heterocycles in the 3-position that modulate and/or inhibit cell proliferation, such as the activity of protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating CDK dependent diseases to modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer as well as other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

  描述了在3-位置带有取代氮的5-成员杂环的3,5-二取代吲唑化合物，这些化合物调节和/或抑制细胞增殖，如蛋白激酶活性。这些化合物和含有它们的药物组合物能够调节和/或抑制介导CDK依赖性疾病的不需要的细胞增殖。该发明还涉及含有这些化合物的药物组合物的治疗或预防用途，以及通过给予这些化合物的有效量来治疗癌症以及与不需要的血管生成和/或细胞增殖相关的其他疾病状态，如糖尿病视网膜病变、新生血管性青光眼、类风湿性关节炎和牛皮癣的方法。
• Indazole compounds, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation
  申请人：——

  公开号：US20020161022A1

  公开（公告）日：2002-10-31

  Indazole compounds that modulate and/or inhibit cell proliferation, such as the activity of protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating, e.g., kinases-dependent diseases to modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer as well as other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

  描述了调节和/或抑制细胞增殖的吲唑化合物，例如蛋白激酶活性。这些化合物和含有它们的药物组合物能够介导，例如，依赖激酶的疾病，以调节和/或抑制不需要的细胞增殖。该发明还涉及含有这些化合物的药物组合物的治疗或预防用途，以及通过给予这些化合物的有效量来治疗癌症以及与不需要的血管生成和/或细胞增殖相关的其他疾病状态，如糖尿病视网膜病变、新生血管性青光眼、类风湿性关节炎和牛皮癣的方法。
• [EN] IMIDAZOLE DERIVATIVES AND THEIR USE AS MODULATORS OF CYCLIN DEPENDENT KINASES<br/>[FR] DÉRIVÉS D'IMIDAZOLE ET LEUR UTILISATION COMME MODULATEURS DES KINASES DÉPENDANTES DES CYCLINES
  申请人：NOVARTIS AG

  公开号：WO2010125402A1

  公开（公告）日：2010-11-04

  The invention provides compounds of the formula (I): and salts, tautomers, solvates and N-oxides thereof; wherein Q is CH or N; X is N, N+-O- or CR3; Y is N, N+-O- or CR3a; R1 and R2 are independently selected from hydrogen and various substituents as defined in the claims; or R1 and R2 together with the atoms to which they are attached, link to form an optionally substituted carbocyclic or heterocyclic aromatic or non-aromatic ring of 4 to 7 members; R3 is selected from hydrogen and various substituents; and R3a is selected from hydrogen and various substituents as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds. The compounds of formula (I) have activity as inhibitors of CDK kinases and are useful in the treatment of inter alia proliferative diseases such as cancers.

  该发明提供了式(I)的化合物及其盐、互变异构体、溶剂合物和N-氧化物；其中Q为CH或N；X为N、N+-O-或CR3；Y为N、N+-O-或CR3a；R1和R2分别选自氢和各种定义中的取代基；或R1和R2与它们连接的原子一起，形成一个可选择地取代的含氢碳环或杂环芳香或非芳香环，成员数为4到7；R3选自氢和各种取代基；R3a选自氢和各种定义中的取代基。还提供了含有式(I)的化合物的药物组合物，制备该化合物的方法以及该化合物的医药用途。式(I)的化合物具有作为CDK激酶抑制剂的活性，并可用于治疗癌症等增殖性疾病。
• [EN] 3,5 DISUBSTITUTED INDAZOLE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS FOR MEDIATING OR INHIBITING CELL PROLIFERATION<br/>[FR] COMPOSES D'INDAZOLE 3,5 DISUBSTITUTES, COMPOSITIONS PHARMACEUTIQUES, ET PROCEDES POUR MEDIER OU INHIBER LA PROLIFERATION CELLULAIRE
  申请人：PFIZER

  公开号：WO2005009997A1

  公开（公告）日：2005-02-03

  3,5 disubstituted indazole compounds that modulate and/or inhibit cell proliferation, such as the activity of protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating CDK dependent diseases to modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer as well as other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

  描述了能够调节和/或抑制细胞增殖的3,5-二取代吲唑化合物，例如蛋白激酶的活性。这些化合物和含有它们的药物组合物能够通过调节和/或抑制不需要的细胞增殖来调解CDK依赖性疾病。本发明还涉及含有这些化合物的药物组合物的治疗或预防用途，以及通过给予这些化合物的有效量来治疗癌症以及与不需要的血管生成和/或细胞增殖相关的其他疾病状态，如糖尿病性视网膜病变、新生血管性青光眼、类风湿性关节炎和牛皮癣等。
• INDAZOLES AS WNT/B-CATENIN SIGNALING PATHWAY INHIBITORS AND THERAPEUTIC USES THEREOF
  申请人：Hood John

  公开号：US20110034441A1

  公开（公告）日：2011-02-10

  Described herein are methods of treating a disorder or disease in which aberrant Wnt signaling is implicated, with a variety of compounds, including Wnt inhibitor compounds. More particularly, it concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases due to mutations in Wnt signaling components.

  本文描述了一种治疗与异常Wnt信号传导有关的疾病或紊乱的方法，使用各种化合物，包括Wnt抑制剂化合物。更具体地，涉及使用吲唑化合物或其类似物治疗由Wnt途径信号激活所特征的疾病（如癌症、异常细胞增殖、血管生成、阿尔茨海默病和骨关节炎），调节由Wnt途径信号介导的细胞事件，以及由于Wnt信号传导组分突变引起的遗传疾病。