3-amino-N-(2-aminoethyl)-2,2-bis(naphthalen-2-ylmethyl)propanamide | 1262851-74-0

• 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: 3-amino-N-(2-aminoethyl)-2,2-bis(naphthalen-2-ylmethyl)propanamide
• 英文别名: N-(2-aminoethyl)-2-(aminomethyl)-3-naphthalen-2-yl-2-(naphthalen-2-ylmethyl)propanamide
• CAS: 1262851-74-0
• 化学式: C₂₇H₂₉N₃O
• 分子量: 411.547
• InChiKey: ZOSLLLKFQJEPRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  81.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-[[(2-Methylpropan-2-yl)oxycarbonylamino]methyl]-3-naphthalen-2-yl-2-(naphthalen-2-ylmethyl)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(naphthalen-2-ylmethyl)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

• 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。
• THERAPEUTIC PEPTIDES
  申请人：Strom Morten

  公开号：US20130035296A1

  公开（公告）日：2013-02-07

  The present invention provides a peptide, peptidomimetic or amino acid derivative having a net positive charge of at least +2 and incorporating a disubstituted β amino acid, each of the substituting groups in the β amino acid, which may be the same or different, comprises at least (7) non-hydrogen atoms, is lipophilic and has at least one cyclic group, one or more cyclic groups within a substituting group may be linked or fused to one or more cyclic groups within the other substituting group and where cyclic groups are fused in this way the combined total number of non-hydrogen atoms for the two substituting groups is at least (12), for use as a cytolytic therapeutic agent; as well as non therapeutic uses of these molecules and certain defined novel compounds from within this definition.

  本发明提供了一种具有至少+2的净正电荷并且包含二取代β氨基酸的肽、肽类似物或氨基酸衍生物，β氨基酸中的每个取代基（可能相同也可能不同）包括至少（7）个非氢原子，具有亲脂性并且至少有一个环状基团，一个或多个取代基内的环状基团可以连接或融合到另一个取代基内的一个或多个环状基团中，当环状基团以这种方式融合时，两个取代基的非氢原子的总数至少为（12），用作溶细胞治疗剂；以及这些分子的非治疗用途以及从该定义中确定的某些新化合物。
• US8809280B2
  申请人：——

  公开号：US8809280B2

  公开（公告）日：2014-08-19