Methyl 2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-3-naphthalen-2-yl-2-(naphthalen-2-ylmethyl)propanoate | 1202779-09-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: Methyl 2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-3-naphthalen-2-yl-2-(naphthalen-2-ylmethyl)propanoate
• CAS: 1202779-09-6
• 化学式: C₃₁H₃₃NO₄
• 分子量: 483.607
• InChiKey: JISLERSEBHBPKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-3-naphthalen-2-yl-2-(naphthalen-2-ylmethyl)propanoate 在 lithium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 18.0h， 以80%的产率得到2-[[(2-Methylpropan-2-yl)oxycarbonylamino]methyl]-3-naphthalen-2-yl-2-(naphthalen-2-ylmethyl)propanoic acid
  参考文献：
  名称：

  Antimicrobial Activity of Small β-Peptidomimetics Based on the Pharmacophore Model of Short Cationic Antimicrobial Peptides

  摘要：

  We have synthesized a series of small beta-peptidomimetics (M-w < 650) that were based on the minimal pharmacophore model for anti-Staphylococcal activity of short cationic antimicrobial peptides. All beta-peptidomimetics had a net charge of +2 and formed an amphipathic scaffold consisting of an achiral lipophilic beta(2,2)-amino acid coupled to a C-terminal L-arginine amide residue. By varying the lipophilic side-chains of the beta(2,2)-amino acids, we obtained a series of highly potent beta-peptidomimetics with high enzymatic stability against alpha-chymotrypsin and a general low toxicity against human erythrocytes. The most potent beta-peptidomimetics displayed minimal inhibitory concentrations of 2.1-7.2 mu M against Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant Staphylococcus epidermidis (MRSE), and Escherichia coli, Small amphipathic beta-peptidomimetics may be a promising class of antimicrobial agents by means of having a similar range of potency and selectivity as larger cationic antimicrobial peptides in addition to improved enzymatic stability and lower costs of production.

  DOI：

  10.1021/jm901052r
• 作为产物：
  描述：

  methyl 2-cyano-3-(2-naphthyl)-2-[(2-naphthyl)methyl]propionate 在 氢气 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 138.0h， 生成 Methyl 2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-3-naphthalen-2-yl-2-(naphthalen-2-ylmethyl)propanoate
  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 Small β-Peptidomimetics Based on the Pharmacophore Model of Short Cationic Antimicrobial Peptides
  作者：Terkel Hansen、Tore Alst、Martina Havelkova、Morten B. Strøm

  DOI：10.1021/jm901052r

  日期：2010.1.28

  We have synthesized a series of small beta-peptidomimetics (M-w < 650) that were based on the minimal pharmacophore model for anti-Staphylococcal activity of short cationic antimicrobial peptides. All beta-peptidomimetics had a net charge of +2 and formed an amphipathic scaffold consisting of an achiral lipophilic beta(2,2)-amino acid coupled to a C-terminal L-arginine amide residue. By varying the lipophilic side-chains of the beta(2,2)-amino acids, we obtained a series of highly potent beta-peptidomimetics with high enzymatic stability against alpha-chymotrypsin and a general low toxicity against human erythrocytes. The most potent beta-peptidomimetics displayed minimal inhibitory concentrations of 2.1-7.2 mu M against Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant Staphylococcus epidermidis (MRSE), and Escherichia coli, Small amphipathic beta-peptidomimetics may be a promising class of antimicrobial agents by means of having a similar range of potency and selectivity as larger cationic antimicrobial peptides in addition to improved enzymatic stability and lower costs of production.
• Synthesis of Cationic Antimicrobial β^2,2-Amino Acid Derivatives with Potential for Oral Administration
  作者：Terkel Hansen、Dominik Ausbacher、Gøril E. Flaten、Martina Havelkova、Morten B. Strøm

  DOI：10.1021/jm101327d

  日期：2011.2.10

  We have prepared a series of highly potent achiral cationic beta(2,2)-amino acid derivatives that fulfill the Lipinski's rule of five and that contain the basic structural requirements of short cationic antimicrobial peptides. Highest antimicrobial potency was observed for one of the smallest beta(2,2)-amino acid derivatives (M-w 423.6) exhibiting a MIC of 3.8 mu M against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and Staphylococcus aureus, and 7.7 mu M against Escherichia coli. The beta(2,2)-amino acid derivatives were shown to have similar absorption properties as several commercially available drugs, and the results implied a resembling membrane disrupting mechanism of action as reported for much larger cationic antimicrobial peptides. By their high potency, nontoxicity, absorption properties, and ease of synthesis, the beta(2,2)-amino acid derivatives demonstrate a way to modify a vastly investigated class of cationic antimicrobial peptides into small drug-like molecules with high commercial potential.
• 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.