tert-butyl 4-(5-ethylpyrimidin-2-yl)piperazin-1-carboxylate | 501126-08-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(5-ethylpyrimidin-2-yl)piperazin-1-carboxylate
• 英文别名: tert-butyl 4-(5-ethylpyrimidin-2-yl)piperazine-1-carboxylate
• CAS: 501126-08-5
• 化学式: C₁₅H₂₄N₄O₂
• 分子量: 292.381
• InChiKey: HWGWISRVEWQRIQ-UHFFFAOYSA-N

物化性质

• 熔点：
  67-68 °C
• 沸点：
  432.7±55.0 °C(Predicted)
• 密度：
  1.127±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(5-ethylpyrimidin-2-yl)piperazin-1-carboxylate 在 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 D-750905
  参考文献：
  名称：

  Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives

  摘要：

  Protein kinases play several pertinent roles in cell proliferation, and targeting these proteins has been shown to be a successful strategy toward controlling different malignancies. Despite the great discovery stories during the last two decades, there is still a demand for anticancer small molecules with the potential of being selective on both the protein kinase and/or the cellular level. A series of novel piperazinylpyrimidine compounds were synthesized and tested for their potential to selectively inhibit the growth of certain tumor cell lines included within the NCI-60 cell line panel. MDA-MB-468, a triple-negative/basal-like breast carcinoma, cell line was among the most sensitive cell lines towards compounds 4 and 15. The three most interesting compounds identified in cellular screens (4, 15, and 16) were subjected to kinase profiling and found to have an interesting selective tendency to target certain kinase subfamily members; PDGFR, CK1, RAF and others. Compound 4 showed a selective tendency to bind to and/or inhibit the function of certain KIT and PDGFRA mutants compared to their wild-type isoforms. Piperazinylpyrimidine based derivatives represent a new class of selective kinase inhibitors. Significantly 4 is more potent at inhibiting oncogenic mutant forms of PDGFR family kinases, which is relevant in terms of its potential use in treating tumors that have become resistant to treatment or driven by such mutations. The clinical demand for agents useful in the control of triple-negative/basal-like breast cancer justifies our interest in compound 15 which is a potent growth inhibitor of MDA-MB-468 cell line. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.057
• 作为产物：
  描述：

  2-氯-5-乙基嘧啶 、 N-Boc-哌嗪 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 tert-butyl 4-(5-ethylpyrimidin-2-yl)piperazin-1-carboxylate
  参考文献：
  名称：

  黄嘌呤衍生物的最优化可产生作为靶向DPP-IV和GPR119的强效双配体的HBK001盐酸盐。

  摘要：

  通过成环策略发现了一系列源自先前命中的20i的黄嘌呤化合物，它们在末端侧链上进行了修饰。对疏水侧链中带有刚性杂环的化合物的系统优化导致了新的先导化合物HBK001（21h），其具有改进的DPP-IV抑制作用和体外适度的GPR119激动活性。为了进一步研究PK和PD谱图，我们继续以克为单位合成21h及其盐酸盐（22），并通过ADME / T和口服糖耐量试验（OGTT）对ICR小鼠进行了评估。与其游离碱21h相比，化合物22在体内显示出改善的生物利用度和降低血糖的作用，这可能归因于其溶解度和渗透性的改善。对化合物22的初步毒性研究表明，mini-Ames的结果为阴性，小鼠的初步急性毒性LD50高于1.5 g / kg，而对hERG通道的抑制作用中等，IC50为4.9μM，可能是由于其高亲脂性。这些发现对于将来针对更有效，更安全的靶向DPP-IV和GPR119的双配体治疗糖尿病的药物设计将是有用的。

  DOI：

  10.1016/j.ejmech.2019.112017

文献信息

• [EN] NOVEL TRIAZOLONE DERIVATIVES OR SALTS THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME<br/>[FR] NOUVEAUX DÉRIVÉS DE LA TRIAZOLONE OU LEURS SELS ET COMPOSITION PHARMACEUTIQUE LES COMPRENANT
  申请人：YUHAN CORP

  公开号：WO2014175621A1

  公开（公告）日：2014-10-30

  The present invention provides a triazolone derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The triazolone derivative or its pharmaceutically acceptable salt can effectively activate GPR119; and therefore be usefully applied for preventing or treating diabetes mellitus.

  本发明提供了一种三唑酮衍生物或其药用可接受盐，以及其制备方法和包含其的药物组合物。该三唑酮衍生物或其药用可接受盐可以有效激活GPR119；因此，可用于预防或治疗糖尿病。
• PIPERAZINYLPYRIMIDINE ANALOGUES AS PROTEIN KINASE INHIBITORS
  申请人：RUSSU Wade A.

  公开号：US20120053183A1

  公开（公告）日：2012-03-01

  The invention provides novel compounds based on piperazinylpyrimidine derivatives to be used as protein kinase inhibitors. The compounds may be useful in treating or preventing different cellular proliferation disorders, such as cancer. The present invention also provides methods of preparing these compounds, and methods of using the same.

  该发明提供了基于哌嗪基嘧啶衍生物的新化合物，用作蛋白激酶抑制剂。这些化合物可能在治疗或预防不同的细胞增殖紊乱疾病，如癌症方面具有用处。本发明还提供了制备这些化合物的方法，以及使用这些化合物的方法。
• Pyrrolo pyrimidines as agents for the inhibition of cystein proteases
  申请人：Betschart Claudia

  公开号：US20050054851A1

  公开（公告）日：2005-03-10

  The invention provides compounds of Formula I or a pharmaceutically acceptable salt or ester thereof wherein the symbols have meaning as defined, which are inhibitors of cathepsin K and find use pharmaceutically for treatment of diseases and medical conditions in which cathepsin K is implicated, e.g. various disorders including inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumors.

  本发明提供了I式化合物或其药学上可接受的盐或酯，其中符号的含义如定义所述，它们是猫hepsin K的抑制剂，并在药学上用于治疗猫hepsin K参与的疾病和医疗情况，例如各种疾病，包括炎症、类风湿性关节炎、骨关节炎、骨质疏松和肿瘤。
• Pyrrolo Pyrimidines as Agents for the Inhibition of Cystein Proteases
  申请人：Betschart Claudia

  公开号：US20090054467A1

  公开（公告）日：2009-02-26

  The invention provides compounds of Formula I or a pharmaceutically acceptable salt or ester thereof wherein the symbols have meaning as defined, which are inhibitors of cathepsin K and find use pharmaceutically for treatment of diseases and medical conditions in which cathepsin K is implicated, e.g. various disorders including inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumors.

  本发明提供了公式I的化合物，或其药理学上可接受的盐或酯，其中符号具有定义的含义，这些化合物是卡特普西林K的抑制剂，并在药学上用于治疗与卡特普西林K有关的疾病和医疗条件，例如各种疾病，包括炎症，类风湿性关节炎，骨关节炎，骨质疏松和肿瘤。
• Piperazinylpyrimidine analogues as protein kinase inhibitors
  申请人：Russu Wade A.

  公开号：US08609672B2

  公开（公告）日：2013-12-17

  The invention provides novel compounds based on piperazinylpyrimidine derivatives to be used as protein kinase inhibitors. The compounds may be useful in treating or preventing different cellular proliferation disorders, such as cancer. The present invention also provides methods of preparing these compounds, and methods of using the same.

  本发明提供了基于哌嗪基嘧啶衍生物的新化合物，可用作蛋白激酶抑制剂。这些化合物可用于治疗或预防不同的细胞增殖障碍，例如癌症。本发明还提供了制备这些化合物的方法和使用它们的方法。