tert-butyl 4-(2-chloro-5-nitropyrimidin-4-yl)piperazine-1-carboxylate | 474330-12-6

• 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-(2-chloro-5-nitropyrimidin-4-yl)piperazine-1-carboxylate
• 英文别名: 4-(2-chloro-5-nitro-pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester；4-(2-Chloro-5-nitro-pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester
• CAS: 474330-12-6
• 化学式: C₁₃H₁₈ClN₅O₄
• 分子量: 343.77
• InChiKey: DZPYVGDQEXBDGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-chloro-5-nitropyrimidin-4-yl)piperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 13.0h， 生成 N-(4-morpholinophenyl)-5-nitro-4-(piperazin-1-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Discovery and rational design of 2-aminopyrimidine-based derivatives targeting Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3)

  摘要：

  Herein, with the help of computer-aided drug design (CADD), we describe the structure-based rational drug design, structure-activity relationships, and synthesis of a series of 2-aminopyrimidine derivatives that inhibit both JAK2 and FLT3 kinases. These screening cascades revealed that compound 14l demonstrated the most inhibitory activity with IC₅₀ values of 1.8 and 0.68 nM against JAK2 and FLT3 respectively. 14l also showed potent anti-proliferative activities against HEL (IC₅₀ = 0.84 μM) and Molm-13 (IC₅₀ = 0.019 μM) cell lines, but relatively weak cytotoxicity against K562 and PC-3 cell lines, which proved that it might have high target specificity. In vitro metabolism assay, 14l exhibited moderate stability in RLM (Rat Liver Microsomes) with a half-life time of 31 min. In the cellular context of Molm-13, 14l induced cell cycle arrest in G₁/S phase and enhanced apoptosis in a dose-dependent manner. These results indicate that 14l is a promising dual JAK2/FLT3 inhibitor and worthy of further development.

  DOI：

  10.1016/j.bioorg.2020.104361
• 作为产物：
  描述：

  N-Boc-哌嗪 、 2,4-二氯-5 硝基嘧啶 在 三乙醇胺 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 生成 tert-butyl 4-(2-chloro-5-nitropyrimidin-4-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  Inhibitors of bace

  摘要：

  本发明涉及天冬氨酸蛋白酶抑制剂，特别是BACE。本发明还涉及其组合物和方法，用于在哺乳动物中抑制BACE活性，并用于治疗阿尔茨海默病和其他BACE介导的疾病。

  公开号：

  US20030095958A1

文献信息

• INHIBITORS OF BACE
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1389194A2

  公开（公告）日：2004-02-18
• [EN] INHIBITORS OF BACE<br/>[FR] INHIBITEURS DE BACE
  申请人：VERTEX PHARMA

  公开号：WO2002088101A2

  公开（公告）日：2002-11-07

  The present invention relates to inhibitors of aspartic proteinases, particularly, BACE. The present invention also relates to compositions thereof and methods therewith for inhibiting BACE activity in a mammal, and for treating Alzheimer's Disease and other BACE-mediated diseases.
• Inhibitors of bace
  申请人：——

  公开号：US20030095958A1

  公开（公告）日：2003-05-22

  The present invention relates to inhibitors of aspartic proteinases, particularly, BACE. The present invention also relates to compositions thereof and methods therewith for inhibiting BACE activity in a mammal, and for treating Alzheimer's Disease and other BACE-mediated diseases.

  本发明涉及天冬氨酸蛋白酶抑制剂，特别是BACE。本发明还涉及其组合物和方法，用于在哺乳动物中抑制BACE活性，并用于治疗阿尔茨海默病和其他BACE介导的疾病。
• Discovery and rational design of 2-aminopyrimidine-based derivatives targeting Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3)
  作者：Yingxiu Li、Peng Wang、Cong Chen、Tianyu Ye、Yufei Han、Yunlei Hou、Yajing Liu、Ping Gong、Mingze Qin、Yanfang Zhao

  DOI：10.1016/j.bioorg.2020.104361

  日期：2020.11

  Herein, with the help of computer-aided drug design (CADD), we describe the structure-based rational drug design, structure-activity relationships, and synthesis of a series of 2-aminopyrimidine derivatives that inhibit both JAK2 and FLT3 kinases. These screening cascades revealed that compound 14l demonstrated the most inhibitory activity with IC₅₀ values of 1.8 and 0.68 nM against JAK2 and FLT3 respectively. 14l also showed potent anti-proliferative activities against HEL (IC₅₀ = 0.84 μM) and Molm-13 (IC₅₀ = 0.019 μM) cell lines, but relatively weak cytotoxicity against K562 and PC-3 cell lines, which proved that it might have high target specificity. In vitro metabolism assay, 14l exhibited moderate stability in RLM (Rat Liver Microsomes) with a half-life time of 31 min. In the cellular context of Molm-13, 14l induced cell cycle arrest in G₁/S phase and enhanced apoptosis in a dose-dependent manner. These results indicate that 14l is a promising dual JAK2/FLT3 inhibitor and worthy of further development.