(S,S,S)-{2-[1-(1-tert-butylcarbamoyl-2-methylpropylcarbamoyl)-2-methylbutylcarbamoyl]pyrrolidin-1-yl}carbamic acid tert-butyl ester | 1166398-91-9

• 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)-{2-[1-(1-tert-butylcarbamoyl-2-methylpropylcarbamoyl)-2-methylbutylcarbamoyl]pyrrolidin-1-yl}carbamic acid tert-butyl ester
• CAS: 1166398-91-9
• 化学式: C₂₅H₄₇N₅O₅
• 分子量: 497.679
• InChiKey: LWRVVRMWUBODOT-VJANTYMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  35.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  128.87
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S,S,S)-{2-[1-(1-tert-butylcarbamoyl-2-methylpropylcarbamoyl)-2-methylbutylcarbamoyl]pyrrolidin-1-yl}carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 反应 2.0h， 生成
  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
• 作为产物：
  描述：

  L-Valinamide, L-isoleucyl-N-(1,1-dimethylethyl)- 、 (S)-(-)-N-BOC-L-脯氨酸肼 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 以78%的产率得到(S,S,S)-{2-[1-(1-tert-butylcarbamoyl-2-methylpropylcarbamoyl)-2-methylbutylcarbamoyl]pyrrolidin-1-yl}carbamic acid tert-butyl ester
  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