5-benzyl-2-(piperazin-1-yl)pyrimidine | 1283119-10-7

• 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: 5-benzyl-2-(piperazin-1-yl)pyrimidine
• 英文别名: 5-benzyl-2-piperazin-1-ylpyrimidine
• CAS: 1283119-10-7
• 化学式: C₁₅H₁₈N₄
• 分子量: 254.335
• InChiKey: MWMUMWHCKAQCQM-UHFFFAOYSA-N

物化性质

• 熔点：
  108-110 °C
• 沸点：
  443.0±55.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-benzyl-2-(piperazin-1-yl)pyrimidine 在 iron sulfide 、 三乙酰氧基硼氢化钠 、 氯化铵 作用下， 以 甲醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 12.0h， 生成 2-(4-(3-aminobenzyl)piperazin-1-yl)-5-benzylpyrimidine
  参考文献：
  名称：

  Anti-tumor pyrimidinylpiperazines bind to the prosurvival Bcl-2 protein family member Bcl-XL

  摘要：

  Overexpression of prosurvival or underexpression of pro-death Bcl-2 family proteins can lead to cancer cell resistance to chemotherapy and radiation treatment. Inhibition of the prosurvival Bcl-2 family proteins has become a strategy for cancer therapy and inhibitors are currently being evaluated in the clinic both as single agents and in combination with established drugs. Here we describe the design, synthesis, and evaluation of pyrimidylpiperazines that were discovered to be inhibitors of the prosurvival Bcl-2 protein family member Bcl-XL. This study identified compound 21 which demonstrated a GI(50) value of 8.4 mu M against A549 lung adenocarcinoma cells and a binding affinity K-i value for Bcl-XL of 127 nM. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.054
• 作为产物：
  描述：

  B-苄基-9-硼杂双环[3.3.1]壬烷 在 盐酸 、 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 12.0h， 生成 5-benzyl-2-(piperazin-1-yl)pyrimidine
  参考文献：
  名称：

  Anti-tumor pyrimidinylpiperazines bind to the prosurvival Bcl-2 protein family member Bcl-XL

  摘要：

  Overexpression of prosurvival or underexpression of pro-death Bcl-2 family proteins can lead to cancer cell resistance to chemotherapy and radiation treatment. Inhibition of the prosurvival Bcl-2 family proteins has become a strategy for cancer therapy and inhibitors are currently being evaluated in the clinic both as single agents and in combination with established drugs. Here we describe the design, synthesis, and evaluation of pyrimidylpiperazines that were discovered to be inhibitors of the prosurvival Bcl-2 protein family member Bcl-XL. This study identified compound 21 which demonstrated a GI(50) value of 8.4 mu M against A549 lung adenocarcinoma cells and a binding affinity K-i value for Bcl-XL of 127 nM. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.054

文献信息

• COMPOSITIONS USEFUL FOR TREATING DISORDERS RELATED TO KIT
  申请人：Hodous Brian L.

  公开号：US20150111857A1

  公开（公告）日：2015-04-23

  Compounds and compositions useful for treating disorders related to KIT and PDFGR are described herein.

  这里描述了用于治疗与KIT和PDFGR相关疾病的化合物和组合物。
• [EN] PIPERAZINE DERIVATIVES AND THEIR USE AS KIT MODULATORS<br/>[FR] DÉRIVÉS DE PIPÉRAZINE ET LEUR UTILISATION COMME MODULATEURS DE KIT
  申请人：BLUEPRINT MEDICINES CORP

  公开号：WO2014160521A1

  公开（公告）日：2014-10-02

  Compounds having structural formula (I) : or a pharmaceutically acceptable salt or a tautomer thereof or having structural formula (III) : or a pharmaceutically acceptable salt or tautomer thereof useful for treating disorders related to Kit are described herein.

  具有结构式（I）的化合物：或其药学上可接受的盐或互变异构体，或具有结构式（III）的化合物：或其药学上可接受的盐或互变异构体，用于治疗与Kit相关的疾病。
• 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。
• Compositions useful for treating disorders related to kit
  申请人：Hodous Brian L.

  公开号：US09334263B2

  公开（公告）日：2016-05-10

  Compounds and compositions useful for treating disorders related to KIT and PDFGR are described herein.

  本文描述了用于治疗与KIT和PDFGR相关的疾病的化合物和组合物。
• Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives
  作者：Hassan M. Shallal、Wade A. Russu

  DOI：10.1016/j.ejmech.2011.02.057

  日期：2011.6

  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.