(E)-4-(2-butoxyvinyl)-2-chloro-5-fluoropyrimidine | 1224708-13-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (E)-4-(2-butoxyvinyl)-2-chloro-5-fluoropyrimidine
• 英文别名: 4-[(E)-2-butoxyethenyl]-2-chloro-5-fluoropyrimidine
• CAS: 1224708-13-7
• 化学式: C₁₀H₁₂ClFN₂O
• 分子量: 230.669
• InChiKey: QRJHAXOKINEHEZ-GQCTYLIASA-N

物化性质

• 沸点：
  355.3±27.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-4-(2-butoxyvinyl)-2-chloro-5-fluoropyrimidine 在 Oxone 、 potassium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-(2-methoxy-5-nitrophenyl)-5-(methylsulfinyl)-4-(pyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Structure- and Reactivity-Based Development of Covalent Inhibitors of the Activating and Gatekeeper Mutant Forms of the Epidermal Growth Factor Receptor (EGFR)

  摘要：

  A novel series of small-molecule inhibitors has been developed to target the double mutant form of the epidermal growth factor receptor (EGFR) tyrosine kinase, which is resistant to treatment with gefitinib and erlotinib. Our reported compounds also show selectivity over wild-type EGFR. Guided by molecular modeling, this series was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and demonstrates high levels of activity in cellular models of the double mutant form of EGFR. In addition, these compounds show significant activity against the activating mutations, which gefitinib and erlotinib target and inhibition of which gives rise to their observed clinical efficacy. A glutathione (GSH)-based assay was used to measure thiol reactivity toward the electrophilic functionality of the inhibitor series, enabling both the identification of a suitable reactivity window for their potency and the development of a reactivity quantitative structure-property relationship (QSPR) to support design.

  DOI：

  10.1021/jm400822z
• 作为产物：
  描述：

  乙烯基正丁醚 、 2,4-二氯-5-氟嘧啶 在 palladium diacetate 、 三乙胺 作用下， 以41 %的产率得到(E)-4-(2-butoxyvinyl)-2-chloro-5-fluoropyrimidine
  参考文献：
  名称：

  细胞周期蛋白依赖性激酶 7 和 9 强效抑制剂的发现：设计、合成、构效关系分析和生物学评价

  摘要：

  两个靶点：4-(咪唑并[1,2- a ]嘧啶-3-基)- N -吡啶基嘧啶-2-胺被发现不仅是细胞周期蛋白依赖性激酶 (CDK) 7 和 9 的有效抑制剂，而且还有效针对一系列人类癌细胞系的抗增殖剂。细胞机制研究的结果支持观察到的抗增殖作用可能源于两种 CDK 的抑制。该手稿的先前版本已存放在预印本服务器上 (https://doi.org/10.2139/ssrn.4210989 ).

  DOI：

  10.1002/cmdc.202200582

文献信息

• [EN] DERIVATIVES OF 4-(IMIDAZO[1,2-A]PYRIDIN-3-YL)-N-(PYRIDIN-3-YL) PYRIMIDIN-2- AMINE FOR TREATING PROLIFERATIVE DISEASES AND CONDITIONS<br/>[FR] DÉRIVÉS DE 4-(IMIDAZO[1,2-A] PYRIDIN-3-YL)-N-(PYRIDIN-3-YL)PYRIMIDIN-2-AMINE POUR LE TRAITEMENT DE MALADIES ET D'AFFECTIONS PROLIFÉRATIVES
  申请人：AUCENTRA THERAPEUTICS PTY LTD

  公开号：WO2021072475A1

  公开（公告）日：2021-04-22

  A novel class of heteroaryl compounds for use in the prevention and/or treatment of proliferative diseases and conditions including cancers. The compounds are considered to be capable of inhibiting cell proliferation by inhibiting the activity of one or more protein kinases selected from CDKs such as CDK2, CDK4, CDK6 and/or CDK9, and/or other protein kinases such as FLT3 and its mutants. The compounds have the general structure I: (I)

  一类新型的杂环芳基化合物，用于预防和/或治疗包括癌症在内的增殖性疾病和症状。这些化合物被认为能够通过抑制细胞增殖来抑制细胞蛋白激酶的活性，所选的蛋白激酶包括CDKs（如CDK2、CDK4、CDK6和/或CDK9）以及其他蛋白激酶，如FLT3及其突变体。这些化合物具有一般结构I：（I）
• [EN] DERIVATIVES OF 4-(IMIDAZO[L,2-A]PYRIDIN-3-YL)-N-(PYRIDINYL)PYRIMIDIN- 2-AMINE AS THERAPEUTIC AGENTS<br/>[FR] DÉRIVÉS DE 4-(IMIDAZO [L, 2-A] PYRIDINE-3-YL)-N-(PYRIDINYL) PYRIMIDINE-2-AMINE EN TANT QU'AGENTS THÉRAPEUTIQUES
  申请人：AUCENTRA THERAPEUTICS PTY LTD

  公开号：WO2021003517A1

  公开（公告）日：2021-01-14

  A novel class of heteroaryl compounds for use in the prevention and/or treatment of proliferative diseases and conditions including cancers. The compounds are considered to be capable of inhibiting cell proliferation by inhibiting the activity of FLT3 and its mutant forms and/or other protein kinases such as CDKs. The compounds have the general structure I:

  一类新型的杂环芳基化合物，用于预防和/或治疗包括癌症在内的增生性疾病和症状。这些化合物被认为能够通过抑制FLT3及其突变形式和/或其他蛋白激酶如CDK的活性来抑制细胞增殖。这些化合物具有一般结构I：
• NOVEL COMPOUNDS 515
  申请人：Ducray Richard

  公开号：US20100105655A1

  公开（公告）日：2010-04-29

  There is provided novel pyrimidine derivatives of formula (I) or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

  提供了化学式（I）的新型嘧啶衍生物或其药用盐，以及它们的制备方法、含有它们的药物组合物以及它们在治疗中的应用。
• Imidazopyridazine compound
  申请人：HANMI PHARMACEUTICAL CO., LTD.

  公开号：US10781217B2

  公开（公告）日：2020-09-22

  The present invention relates to an imidazopyridazine compound having cell growth inhibitory activity, and a pharmaceutical composition for preventing or treating cancer or a tumor including the same. The imidazopyridazine compound of Chemical Formula 1 according to the present invention has excellent cell growth inhibitory activity, and thus can be favorably used as a preventive or therapeutic agent for cancer or a tumor.

  本发明涉及一种具有细胞生长抑制活性的咪唑哒嗪化合物，以及包括其在内的一种用于预防或治疗癌症或肿瘤的药物组合物。根据本发明的化学式 1 的咪唑哒嗪化合物具有极佳的细胞生长抑制活性，因此可用作癌症或肿瘤的预防或治疗剂。
• Derivatives of N-cycloalkyl/heterocycloalkyl-4-(imidazo[1,2-a]pyridine)pyrimidin-2-amine as therapeutic agents
  申请人：Aucentra Therapeutics Pty Ltd

  公开号：US11111245B2

  公开（公告）日：2021-09-07

  A novel class of inhibitors of protein kinases that are useful in the treatment of cell proliferative diseases and conditions, and especially those characterised by over-expression of one or more CDK enzyme and/or by one or more aberrant CDK activity, including certain cancers of lung, breast, brain, ovary, prostate, colorectal cancer and leukaemias. The inhibitors have the general structure (I).

  一类新型蛋白激酶抑制剂，可用于治疗细胞增殖性疾病和病症，特别是以一种或多种 CDK 酶过度表达和/或一种或多种 CDK 活性异常为特征的疾病和病症，包括某些肺癌、乳腺癌、脑癌、卵巢癌、前列腺癌、结直肠癌和白血病。这些抑制剂具有一般结构 (I)。