5-[[6-Amino-1-[[1-[(3-amino-3-oxopropyl)-[3-(4-bromophenyl)propylcarbamoyl]amino]-4-carboxybutan-2-yl]-[2-(4-bromophenyl)ethylcarbamoyl]amino]hexan-2-yl]-(3-cyclohexylpropylcarbamoyl)amino]-4-(phenylcarbamoylamino)pentanoic acid | 1204199-42-7

• 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: 5-[[6-Amino-1-[[1-[(3-amino-3-oxopropyl)-[3-(4-bromophenyl)propylcarbamoyl]amino]-4-carboxybutan-2-yl]-[2-(4-bromophenyl)ethylcarbamoyl]amino]hexan-2-yl]-(3-cyclohexylpropylcarbamoyl)amino]-4-(phenylcarbamoylamino)pentanoic acid
• CAS: 1204199-42-7
• 化学式: C₅₅H₈₀Br₂N₁₀O₉
• 分子量: 1185.11
• InChiKey: SNZPICQSGNGTHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  76
• 可旋转键数：
  34
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  282
• 氢给体数：
  9
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  5-[[6-Amino-1-[[1-[(3-amino-3-oxopropyl)-[3-(4-bromophenyl)propylcarbamoyl]amino]-4-carboxybutan-2-yl]-[2-(4-bromophenyl)ethylcarbamoyl]amino]hexan-2-yl]-(3-cyclohexylpropylcarbamoyl)amino]-4-(cyclohexylmethylcarbamoylamino)pentanoic acid 在 三异丙基硅烷 、 水 、 三氟乙酸 作用下， 反应 2.0h， 生成 5-[[6-Amino-1-[[1-[(3-amino-3-oxopropyl)-[3-(4-bromophenyl)propylcarbamoyl]amino]-4-carboxybutan-2-yl]-[2-(4-bromophenyl)ethylcarbamoyl]amino]hexan-2-yl]-(3-cyclohexylpropylcarbamoyl)amino]-4-(phenylcarbamoylamino)pentanoic acid
  参考文献：
  名称：

  N-Acylpolyamine inhibitors of HDM2 and HDMX binding to p53

  摘要：

  Selective inhibition of protein-protein interactions important for cellular processes could lead to the development of new therapies against disease. In the area of cancer, overexpression of the proteins human double minute 2 (HDM2) and its homolog HDMX has been linked to tumor aggressiveness. Both HDM2 and HDMX bind to p53 and prevent cell cycle arrest or apoptosis in damaged cells. Developing a strategy to simultaneously prevent the binding of both HDM2 and HDMX to p53 is an essential feature of inhibitors to restore p53 activity in a number of different cancers. Inhibition of protein-protein interactions with synthetic molecules is an emerging area of research that requires new inhibitors tailored to mimic the types of interfaces between proteins. Our strategy to create inhibitors of protein-protein interactions is to develop a non-natural scaffold that may be used as a starting point to identify important molecular components necessary for inhibition. In this study, we report an N-acylpolyamine (NAPA) scaffold that supports numerous sidechains in a compact atomic arrangement. NAPAs were constructed by a series of reductive aminations between amino acid derivatives followed by acylation at the resulting secondary amine. An optimized NAPA was able to equally inhibit the association of both HDM2 and HDMX with p53. Our results demonstrate some of the challenges associated with targeting multiple protein-protein interactions involved in overlapping cellular processes. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.10.032