tert-butyl 4-(3-(4-methoxyphenyl)ureido)piperidine-1-carboxylate | 1233952-77-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 4-(3-(4-methoxyphenyl)ureido)piperidine-1-carboxylate
• 英文别名: tert-Butyl 4-[3-(4-methoxyphenyl)ureido]piperidine-1-carboxylate；tert-butyl 4-[(4-methoxyphenyl)carbamoylamino]piperidine-1-carboxylate
• CAS: 1233952-77-6
• 化学式: C₁₈H₂₇N₃O₄
• 分子量: 349.43
• InChiKey: BJQNJRXCSUGROI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-(4-methoxyphenyl)ureido)piperidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-(4-methoxyphenyl)-3-(piperidin-4-yl)urea
  参考文献：
  名称：

  靶向 DOT1L 和 HAT 作为抗白血病药物的腺苷衍生物的设计、合成和生物学评价

  摘要：

  端粒沉默 1 样破坏物 （DOT1L） 是组蛋白赖氨酸甲基转移酶的关键枢纽，也是治疗血液系统恶性肿瘤（包括急性髓性白血病 （AML））的有吸引力的治疗靶点。在这项研究中，我们通过将碱性接头哌啶-4-基甲基基序容纳到相应的芳基脲/苯并咪唑支架上，报道了一系列新的腺苷衍生物作为 DOT1L 抑制剂的设计和合成。抗 DOT1L 酶活性分析表明，化合物 8 、 12 和 13 强烈抑制 DOT1L 活性，IC50 值在所有合成物中为 0.125 至 0.408 μM，并总结了构效关系。此外，化合物 12 通过显著降低细胞中赖氨酸 79 （H3K79me2） 水平的组蛋白 H3 二甲基化，具有相对有效的 DOT1L 抑制活性。随后，针对各种白血病细胞系筛选了所有合成物，表明 DOT1L 活性腺苷衍生物表现出低到中等，而化合物 15 尽管 DOT1L 抑制不成功，但表现出强烈的细胞抑制。因此，认识到化合物

  DOI：

  10.1016/j.bioorg.2024.107771
• 作为产物：
  描述：

  1-Boc-4-氨基哌啶 、 甲氧苯胺 、 对硝基苯基氯甲酸酯 在 三光气 作用下， 以 乙腈 为溶剂， 以88%的产率得到tert-butyl 4-(3-(4-methoxyphenyl)ureido)piperidine-1-carboxylate
  参考文献：
  名称：

  Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles

  摘要：

  The potential of specific proteasome inhibitors to act as anti-cancer agents has attracted intensive investigations. The proteasome can be covalently inhibited by epoxyketone derivatives via a two-step reaction. Several computational approaches have been developed to mimic the covalent binding event. Compound 1 composed of a six-membered heterocyclic ring was designed by using covalent docking. With a possible different binding mode from the clinical compound Carfilzomib, it occupied the 55 pocket of 20S proteasome and showed favorable inhibitory activity. Subsequently optimization and evaluation were taken place. Among these compounds, 11h demonstrated extraordinary in vitro inhibitory activity and selectivity, and good in vivo proteasome inhibitory activity, a favorable pharmacokinetic profile and xenograft tumor inhibition. The possible binding pattern of compound 11h against proteasome was further fully explored via calculations, providing a theoretical basis for finding potent proteasome inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.064

文献信息

• Covalent docking modelling-based discovery of tripeptidyl epoxyketone proteasome inhibitors composed of aliphatic-heterocycles
  作者：Xiao-Wu Dong、Jian-Kang Zhang、Lei Xu、Jin-Xin Che、Gang Cheng、Xiao-Bei Hu、Li Sheng、An-Hui Gao、Jia Li、Tao Liu、Yong-Zhou Hu、Yu-Bo Zhou

  DOI：10.1016/j.ejmech.2018.12.064

  日期：2019.2

  The potential of specific proteasome inhibitors to act as anti-cancer agents has attracted intensive investigations. The proteasome can be covalently inhibited by epoxyketone derivatives via a two-step reaction. Several computational approaches have been developed to mimic the covalent binding event. Compound 1 composed of a six-membered heterocyclic ring was designed by using covalent docking. With a possible different binding mode from the clinical compound Carfilzomib, it occupied the 55 pocket of 20S proteasome and showed favorable inhibitory activity. Subsequently optimization and evaluation were taken place. Among these compounds, 11h demonstrated extraordinary in vitro inhibitory activity and selectivity, and good in vivo proteasome inhibitory activity, a favorable pharmacokinetic profile and xenograft tumor inhibition. The possible binding pattern of compound 11h against proteasome was further fully explored via calculations, providing a theoretical basis for finding potent proteasome inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved.