N-(2-chloropyrimidin-4-yl)-2-methyl-2H-indazol-6-amine | 1262034-87-6

• 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: N-(2-chloropyrimidin-4-yl)-2-methyl-2H-indazol-6-amine
• 英文别名: N-(2-chloropyrimidin-4-yl)-2-methylindazol-6-amine
• CAS: 1262034-87-6
• 化学式: C₁₂H₁₀ClN₅
• 分子量: 259.698
• InChiKey: UJCAFEXIGZWUBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-chloropyrimidin-4-yl)-2-methyl-2H-indazol-6-amine 在 盐酸 、 caesium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 N²-(3-chlorophenyl)-N⁴-methyl-N⁴-(2-methyl-2H-indazol-6-yl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents

  摘要：

  A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by H-1 NMR and MS. Their inhibitory activity against VEGFR-2, PDGFR-alpha and c-kit tyrosine kinases were evaluated. All the compounds exhibited definite kinase inhibition, in which compound 7l was most potent with IC50 values of 12 nM against VEGFR-2. Furthermore, compounds 7c, 7d and 7m demonstrated comparable inhibitory activity against three tyrosine kinases to pazopanib, and compound 7f showed superior inhibitory effects than that of pazopanib. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.003
• 作为产物：
  描述：

  6-硝基吲唑 在 三乙烯二胺 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.25h， 生成 N-(2-chloropyrimidin-4-yl)-2-methyl-2H-indazol-6-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents

  摘要：

  A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by H-1 NMR and MS. Their inhibitory activity against VEGFR-2, PDGFR-alpha and c-kit tyrosine kinases were evaluated. All the compounds exhibited definite kinase inhibition, in which compound 7l was most potent with IC50 values of 12 nM against VEGFR-2. Furthermore, compounds 7c, 7d and 7m demonstrated comparable inhibitory activity against three tyrosine kinases to pazopanib, and compound 7f showed superior inhibitory effects than that of pazopanib. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.003

文献信息

• 4-Indazolylamino-2-(2-(indol-3-yl)ethyl)aminopyrimidines useful for the treatment of cancer
  申请人：Chemilia AB

  公开号：EP2711365A1

  公开（公告）日：2014-03-26

  The invention provides novel indazole-substituted diaminopyrimidines of formula I, to methods of preparing such compounds, to pharmaceutical compositions containing such compounds, and to methods for using such compounds in treatment of diseases including cancer; wherein R1-R8 are as defined in the specification.

  该发明提供了一种新颖的式I的吲唑取代二氨基嘧啶化合物，以及制备这种化合物的方法，包含这种化合物的药物组合物，以及利用这种化合物治疗包括癌症在内的疾病的方法；其中R1-R8如规范中定义。
• Preparation, biological evaluation and QSAR analysis of urea substituted 2,4-diamino-pyrimidine anti-malarials
  作者：Borvornwat Toviwek、Jennifer Riley、Nicole Mutter、Mark Anderson、Lauren Webster、Irene Hallyburton、Duangkamol Gleeson、Kevin D. Read、M. Paul Gleeson

  DOI：10.1039/d2md00218c

  日期：——

  were also undertaken. Compounds 40 demonstrated the best anti-malarial activity at Pf 3D7 (0.09 μM), good selectivity with respect to mammalian cytotoxicity (SI = 54) and low microsomal clearance. Quantitative structure activity relationship (QSAR) analyses point to lipophilicity being a key driver of improved anti-malarial activity. The most active compounds in the series suffered from high lipophilicity

  报道了26 种新的苯脲取代的 2,4-二氨基嘧啶的合成和抗恶性疟原虫( Pf ) 3D7 的评价。制备化合物以提高我们小组先前报道的系列的抗疟活性和选择性。已确定其他特性来评估其作为抗疟疾先导药物的潜力，包括：HepG2 细胞毒性、溶解度、渗透性和亲脂性，以及在人和大鼠微粒体中的体外稳定性。我们还评估了它们对 10 种不同人类激酶的抑制特性。还进行了分子对接、化学信息学和生物信息学分析。化合物40在Pf 3D7 (0.09 μM)下表现出最佳的抗疟活性、对哺乳动物细胞毒性的良好选择性 (SI = 54) 和较低的微粒体清除率。定量结构活性关系（QSAR）分析指出亲脂性是改善抗疟疾活性的关键驱动因素。该系列中最活性的化合物具有高亲脂性、差水溶性和低渗透性。结果提供了有用的信息来指导进一步的化学迭代。
• [EN] METHOD FOR PREPARING PAZOPANIB HYDROCHLORIDE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE CHLORHYDRATE DE PAZOPANIB<br/>[ZH] 帕唑帕尼盐酸盐的制备方法
  申请人：JINAN ASIA PHARMA TECH CO LTD

  公开号：WO2020238220A1

  公开（公告）日：2020-12-03

  本发明属于药物化学合成技术领域，具体涉及一种帕唑帕尼盐酸盐的绿色制备方法。邻甲基苯胺与N-氯代琥珀酰亚胺发生氯代反应得到2-甲基-5-氯-苯胺；再与亚硝酸类化合物反应得到6-氯-2H-吲哚盐酸盐；然后发生N甲基化反应得到N-甲基-6-氯-2H-吲哚；在二甲基亚砜参与下，经过3-位碳原子的烷基化反应得到2，3-二甲基-6-氯-2H-吲唑；再与2-氯-4-氨基-嘧啶和碘甲烷反应得到N-(2-氯嘧啶-4-基)-N-甲基-2，3-二甲基-2H-吲唑-6-胺；最后与3-磺酸胺-4-甲基-苯胺反应得到帕唑帕尼盐酸盐。本发明原料价格低廉，操作简单，操作的危险性低，避免废酸产生，反应收率高、纯度高。
• 4-INDAZOLYLAMINO-2-(2-(INDOL-3-YL)ETHYL)AMINOPYRIMIDINES USEFUL FOR THE TREATMENT OF CANCER
  申请人：Noviga Research AB

  公开号：EP2897951A1

  公开（公告）日：2015-07-29
• [EN] 4-INDAZOLYLAMINO-2-(2-(INDOL-3-YL)ETHYL)AMINOPYRIMIDINES USEFUL FOR THE TREATMENT OF CANCER<br/>[FR] 4-INDAZOLYLAMINO -2- (2- (INDOL-3-YL) ÉTHYL) AMINOPYRIMIDINES UTILES POUR LE TRAITEMENT DU CANCER
  申请人：CHEMILIA AB

  公开号：WO2014044754A1

  公开（公告）日：2014-03-27

  The invention provides novel indazole-substituted diaminopyrimidines of formula I, to methods of preparing such compounds, to pharmaceutical compositions containing such compounds,and to methods for using such compounds in treatment of diseases including cancer; wherein R1-R8 are as defined in the specification.