(S,S,S,S)-1-[1-benzyl-3-(1-benzyl-2-oxoethyl)ureido]pyrrolidine-2-carboxylic acid [1-(1-tert-butylcarbamoyl-2-methylpropylcarbamoyl)-2-methylbutyl]amide | 1166398-97-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S,S,S,S)-1-[1-benzyl-3-(1-benzyl-2-oxoethyl)ureido]pyrrolidine-2-carboxylic acid [1-(1-tert-butylcarbamoyl-2-methylpropylcarbamoyl)-2-methylbutyl]amide
• CAS: 1166398-97-5
• 化学式: C₃₇H₅₄N₆O₅
• 分子量: 662.873
• InChiKey: NGGKHAGFJCYLDC-LJEIBCANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  48.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  139.95
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  (S,S,S,S)-1-[1-benzyl-3-(1-benzyl-2,2-dimethoxyethyl)ureido]pyrrolidine-2-carboxylic acid [1-(1-tert-butylcarbamoyl-2-methylpropylcarbamoyl)-2-methylbutyl]amide 在 三甲基氯硅烷 、 sodium iodide 、 水 、 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以78%的产率得到(S,S,S,S)-1-[1-benzyl-3-(1-benzyl-2-oxoethyl)ureido]pyrrolidine-2-carboxylic acid [1-(1-tert-butylcarbamoyl-2-methylpropylcarbamoyl)-2-methylbutyl]amide
  参考文献：
  名称：

  On the inhibition of HIV-1 protease by hydrazino-ureas displaying the N→CO interaction

  摘要：

  To create novel HIV-1 protease (HIV PR) inhibitors, we have extended our investigations of the N -> C=O interaction as a moiety that reproduces electrostatic properties of the transition state of peptidolysis. Consequently, we prepared a series of compounds with an unusual hydrazino-urea core. In polar protic media, these adopt solely a cyclic constitution displaying the interaction on one side of the molecule while offering a urea moiety on the opposite side meant to hydrogen-bond with the enzyme flaps. Each inhibitor candidate was obtained via a key series of three synthetic steps employing carbonyl-di-imidazole (CDI). It was thus possible to efficiently fuse two independent building blocks, a hydrazine and a protected aminoaldehyde in a convergent manner. NMR and UV analysis proved that all compounds, when dissolved in polar protic media, existed exclusively in the cyclic constitution exhibiting the N -> C=O interaction. In total, five inhibitor candidates were tested with HIV PR for their potency. The one carrying the least bulk in peripheral substituents showed the highest activity. Its very low molecular weight ( 365 g/mol) holds great promise for future improvements in affinity without violating Lipinski's rule of remaining within the limit of 500 g/mol. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.059