3-amino-N-(2-aminoethyl)-2,2-bis(4-(trifluoromethyl)benzyl)propanamide | 1262851-72-8

• 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: 3-amino-N-(2-aminoethyl)-2,2-bis(4-(trifluoromethyl)benzyl)propanamide
• 英文别名: 1-(2-aminoethylamino)-2-(aminomethyl)-3-[4-(trifluoromethyl)phenyl]-2-{[4-(trifluoromethyl)phenyl]methyl}-1-propanone；N-(2-aminoethyl)-2-(aminomethyl)-3-[4-(trifluoromethyl)phenyl]-2-[[4-(trifluoromethyl)phenyl]methyl]propanamide
• CAS: 1262851-72-8
• 化学式: C₂₁H₂₃F₆N₃O
• 分子量: 447.424
• InChiKey: GBYJFMCPBNXWPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.1
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-[[(2-Methylpropan-2-yl)oxycarbonylamino]methyl]-3-[4-(trifluoromethyl)phenyl]-2-[[4-(trifluoromethyl)phenyl]methyl]propanoic acid 在 三异丙基硅烷 、 N,N-二异丙基乙胺 、 fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 170.0h， 生成 3-amino-N-(2-aminoethyl)-2,2-bis(4-(trifluoromethyl)benzyl)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

• Antimicrobial activity of amphipathic α,α-disubstituted β-amino amide derivatives against ESBL – CARBA producing multi-resistant bacteria; effect of halogenation, lipophilicity and cationic character
  作者：Marianne H. Paulsen、Dominik Ausbacher、Annette Bayer、Magnus Engqvist、Terkel Hansen、Tor Haug、Trude Anderssen、Jeanette H. Andersen、Johanna U. Ericson Sollid、Morten B. Strøm

  DOI：10.1016/j.ejmech.2019.111671

  日期：2019.12

  potency and minimize formation of Phase I metabolites. Net positive charge and cationic character of the derivatives had an important effect on toxicity against human cell lines. The most potent and selective derivative was the diguanidine derivative 4e with 3,5-di-brominated benzylic side-chains. Derivative 4e displayed minimum inhibitory concentrations (MIC) of 0.25-8 μg/mL against Gram-positive and Gram-negative

  多重耐药菌的迅速出现和传播已经迫切需要新的抗菌剂。我们在这里报告了一系列两亲性的α，α-二取代的β-氨基酰胺衍生物，具有针对30种革兰氏阳性和革兰氏阴性细菌多耐药临床分离株的活性，包括具有广谱β-内酰胺酶-碳青霉烯酶（ESBL-CARBA）的分离株） 生产。研究了各种卤代芳族侧链，以提高抗菌效力并最大程度减少I相代谢物的形成。衍生物的净正电荷和阳离子特性对其对人细胞系的毒性具有重要影响。最有效和选择性最大的衍生物是具有3，5-二溴苄基侧链的二胍衍生物4e。导数4e的最小抑制浓度（MIC）为0。对革兰氏阳性和革兰氏阴性参考菌株为25-8μg/ mL，对多重耐药的临床分离株为2-32μg/ mL。衍生物4e对人红细胞（EC50> 200μg/ mL），人肝癌细胞（HepG2：EC50> 64μg/ mL）和人肺成纤维细胞（MRC-5：EC50> 64μg/ mL）的毒性也很低毫升）。双胍基衍生
• Efficient and scalable synthesis of α,α-disubstituted β-amino amides
  作者：Marianne Hagensen Paulsen、Magnus Engqvist、Dominik Ausbacher、Morten Bøhmer Strøm、Annette Bayer

  DOI：10.1039/c6ob01219a

  日期：——

  methodology for the preparation of 2-aminoethyl α,α-disubstituted β-amino amides in three steps from methyl cyanoacetate has been developed. The key step in the synthesis was the chemoselective reduction of the nitrile group in presence of an amide and aryl halide functionalities. Reduction with RANEY® Nickel catalyst, either with molecular hydrogen (8–10 bar) or under transfer hydrogenation conditions, necessitated

  已经开发了一种从氰基乙酸甲酯分三步制备2-氨基乙基α，α-二取代的β-氨基酰胺的实用而有效的方法。合成的关键步骤是在酰胺和芳基卤化物官能团存在下腈选择性化学还原。用RANEY®镍催化剂还原，无论是用分子氢（8-10 bar）还是在转移氢化条件下，都需要用Boc 2 O原位保护所得的胺，而用ZnCl 2 / NaBH可以化学选择性地还原含芳基腈的腈。4无脱溴。所开发的方案仅涉及一个色谱纯化步骤，并且可以以克为单位进行。
• 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.