2,2-bis(4-tert-butylbenzyl)-3-guanidino-N-(3-guanidinopropyl)propanamide | 1415983-66-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2,2-bis(4-tert-butylbenzyl)-3-guanidino-N-(3-guanidinopropyl)propanamide
• 英文别名: 2,2-bis[(4-tert-butylphenyl)methyl]-3-(diaminomethylideneamino)-N-[3-(diaminomethylideneamino)propyl]propanamide
• CAS: 1415983-66-2
• 化学式: C₃₀H₄₇N₇O
• 分子量: 521.749
• InChiKey: PUACQFOTGFOYHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  158
• 氢给体数：
  5
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-叔丁基苄溴 在 三异丙基硅烷 、 水 、 氢气 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate 、 三氟乙酸 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 348.0h， 生成 2,2-bis(4-tert-butylbenzyl)-3-guanidino-N-(3-guanidinopropyl)propanamide
  参考文献：
  名称：

  Anticancer activity of small amphipathic β2,2-amino acid derivatives

  摘要：

  We report the anticancer activity from screening of a series of synthetic beta(2,2)-amino acid derivatives that were prepared to confirm the pharmacophore model of short cationic antimicrobial peptides with high anti-Staphylococcal activity. The most potent derivatives against human Burkitt's lymphoma (Ramos) cells displayed IC50 values below 8 mu M, and low toxicity against human red blood cells (EC50 > 200 mu M). A more than 5-fold preference for Ramos cancer cells compared to human lung fibroblasts (MRC-5 cells) was also obtained for the most promising beta(2.2)-amino acid derivative 3-amino-N-(2-aminoethyl)-2,2-bis(naphthalen-2-ylmethyl)propanamide (5c). Screening of 5c at the National Cancer Institute (NCI, USA) confirmed its anticancer potency and revealed a very broad range of anticancer activity with IC50 values of 0.32-3.89 mu M against 59 different cancer cell lines. Highest potency was obtained against the colon cancer cell lines, a non-small cell lung cancer, a melanoma, and three leukemia cell lines included in the NCI screening panel. The reported beta(2,2)-amino acid derivatives constitute a promising new class of anticancer agents based on their high anticancer potency, ease of synthesis, mode-of-action, and optimized pharmacokinetic properties compared to much larger antimicrobial peptides. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.09.048

文献信息

• Anticancer activity of small amphipathic β2,2-amino acid derivatives
  作者：Terkel Hansen、Dominik Ausbacher、Zack G. Zachariassen、Trude Anderssen、Martina Havelkova、Morten B. Strøm

  DOI：10.1016/j.ejmech.2012.09.048

  日期：2012.12

  We report the anticancer activity from screening of a series of synthetic beta(2,2)-amino acid derivatives that were prepared to confirm the pharmacophore model of short cationic antimicrobial peptides with high anti-Staphylococcal activity. The most potent derivatives against human Burkitt's lymphoma (Ramos) cells displayed IC50 values below 8 mu M, and low toxicity against human red blood cells (EC50 > 200 mu M). A more than 5-fold preference for Ramos cancer cells compared to human lung fibroblasts (MRC-5 cells) was also obtained for the most promising beta(2.2)-amino acid derivative 3-amino-N-(2-aminoethyl)-2,2-bis(naphthalen-2-ylmethyl)propanamide (5c). Screening of 5c at the National Cancer Institute (NCI, USA) confirmed its anticancer potency and revealed a very broad range of anticancer activity with IC50 values of 0.32-3.89 mu M against 59 different cancer cell lines. Highest potency was obtained against the colon cancer cell lines, a non-small cell lung cancer, a melanoma, and three leukemia cell lines included in the NCI screening panel. The reported beta(2,2)-amino acid derivatives constitute a promising new class of anticancer agents based on their high anticancer potency, ease of synthesis, mode-of-action, and optimized pharmacokinetic properties compared to much larger antimicrobial peptides. (C) 2012 Elsevier Masson SAS. All rights reserved.