(S)-1-benzyl-3-(1-benzyl-2-oxoethyl)-1-piperidin-1-ylurea | 1044510-11-3

• 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: (S)-1-benzyl-3-(1-benzyl-2-oxoethyl)-1-piperidin-1-ylurea
• 英文别名: 1-benzyl-3-[(2S)-1-oxo-3-phenylpropan-2-yl]-1-piperidin-1-ylurea
• CAS: 1044510-11-3
• 化学式: C₂₂H₂₇N₃O₂
• 分子量: 365.475
• InChiKey: MRMKVDUSMPKGAX-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-氨基哌啶 在 三甲基氯硅烷 、 sodium iodide 、 碘甲烷 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 39.5h， 生成 (S)-1-benzyl-3-(1-benzyl-2-oxoethyl)-1-piperidin-1-ylurea
  参考文献：
  名称：

  Modular construction of quaternary hemiaminal-based inhibitor candidates and their in cellulo assessment with HIV-1 protease

  摘要：

  Non-peptidomimetic drug-like protease inhibitors have potential for circumventing drug resistance. We developed a much-improved synthetic route to our previously reported inhibitor candidate displaying an unusual quaternized hemi-aminal. This functional group forms from a linear precursor upon passage into physiological media. Seven variants were prepared and tested in cellulo with our HIV-1 fusion-protein technology that result in an eGFP-based fluorescent readout. Three candidates showed inhibition potency above 20 mu M and toxicity at higher concentrations, making them attractive targets for further refinement. Importantly, our class of original inhibitor candidates is not recognized by two major multidrug resistance pumps, quite in contrast to most clinically applied HIV-1 protease inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.018

文献信息

• Diversity-Oriented Synthesis of a Drug-Like System Displaying the Distinctive N→C═O Interaction
  作者：Michael Waibel、Jens Hasserodt

  DOI：10.1021/jo800719j

  日期：2008.8.1

  describes the syntheses and characterization of two hydrazino ureas. These fold into a six-membered ring by virtue of the infrequently observed δ+N→C═Oδ− interaction when solvated by polar protic media. The highly polar functional group resulting from this interaction is hypothesized to especially reproduce electronic but also steric features of the transition states of peptide hydrolysis. The urea moiety

  这项研究描述了两种肼基脲的合成和表征。这些凭借很少观察到折叠成六元环δ+ Ñ→C = O δ-被极性质子质子介质溶解时发生相互作用。据推测，由这种相互作用产生的高极性官能团可特别重现肽水解过渡态的电子特征和空间特征。尿素部分构成了现代HIV-1蛋白酶（HIV PR）抑制剂的另一个关键要素，并且意在与酶瓣相互作用。我们已经开发出一种高效，聚合的对映纯化合物合成路线，该路线使用CDI偶联两个独立的构件，一个独立于氨基酸，另一个独立于易获得的肼。因此，为了筛选新的HIV PR抑制剂，需要快速产生多样性。7和8在甲醇中。传递至非极性介质后，观察到完全转化为线性醛形式。
• Modular construction of quaternary hemiaminal-based inhibitor candidates and their in cellulo assessment with HIV-1 protease
  作者：Guillaume Gros、Lorena Martinez、Anna Servat Gimenez、Paula Adler、Philippe Maurin、Roland Wolkowicz、Pierre Falson、Jens Hasserodt

  DOI：10.1016/j.bmc.2013.06.018

  日期：2013.9

  Non-peptidomimetic drug-like protease inhibitors have potential for circumventing drug resistance. We developed a much-improved synthetic route to our previously reported inhibitor candidate displaying an unusual quaternized hemi-aminal. This functional group forms from a linear precursor upon passage into physiological media. Seven variants were prepared and tested in cellulo with our HIV-1 fusion-protein technology that result in an eGFP-based fluorescent readout. Three candidates showed inhibition potency above 20 mu M and toxicity at higher concentrations, making them attractive targets for further refinement. Importantly, our class of original inhibitor candidates is not recognized by two major multidrug resistance pumps, quite in contrast to most clinically applied HIV-1 protease inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.