N^MeAla-Tle-(4-Bzl)Pro-¹Na1-NHCH₂CH₂SH | 1492903-42-0

• 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: N^MeAla-Tle-(4-Bzl)Pro-¹Na1-NHCH₂CH₂SH
• 英文别名: (2S,4R)-4-benzyl-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-N-[(2S)-3-naphthalen-1-yl-1-oxo-1-(2-sulfanylethylamino)propan-2-yl]pyrrolidine-2-carboxamide
• CAS: 1492903-42-0
• 化学式: C₃₇H₄₉N₅O₄S
• 分子量: 659.893
• InChiKey: WQILUXZYHGXIGZ-PSTIANMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  121
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,3,5-三(溴甲基)苯 、 N^MeAla-Tle-(4-Bzl)Pro-¹Na1-NHCH₂CH₂SH 在 四丁基碘化铵 、 caesium carbonate 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 (N^MeAla-Tle-(4-Bzl)Pro-¹Nal-NHCH₂CH₂S)₃-(CH₂)₃Ph
  参考文献：
  名称：

  Novel dimeric Smac analogs as prospective anticancer agents

  摘要：

  A small library of monovalent Smac mimics with general structure NMeAla-Tle-(4R)-4-Benzyl-ProXaa- cysteamide, was synthesized (Xaa = hydrophobic residue). The library was screened in vitro against human breast cancer cell lines MCF-7 and MDA-MB-231, and two most active compounds oligomerized via S-alkylation giving bivalent and trivalent derivatives. The most active bivalent analogue SMAC17-2X was tested in vivo and in physiological conditions (mouse model) it exerted a potent anticancer effect resulting in similar to 23.4 days of tumor growth delay at 7.5 mg/kg dose. Collectively, our findings suggest that bivalent Smac analogs obtained via S-alkylation protocol may be a suitable platform for the development of new anticancer therapeutics. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.024

文献信息

• Novel dimeric Smac analogs as prospective anticancer agents
  作者：Ewa D. Micewicz、Hai T. Luong、Chun-Ling Jung、Alan J. Waring、William H. McBride、Piotr Ruchala

  DOI：10.1016/j.bmcl.2014.02.024

  日期：2014.3

  A small library of monovalent Smac mimics with general structure NMeAla-Tle-(4R)-4-Benzyl-ProXaa- cysteamide, was synthesized (Xaa = hydrophobic residue). The library was screened in vitro against human breast cancer cell lines MCF-7 and MDA-MB-231, and two most active compounds oligomerized via S-alkylation giving bivalent and trivalent derivatives. The most active bivalent analogue SMAC17-2X was tested in vivo and in physiological conditions (mouse model) it exerted a potent anticancer effect resulting in similar to 23.4 days of tumor growth delay at 7.5 mg/kg dose. Collectively, our findings suggest that bivalent Smac analogs obtained via S-alkylation protocol may be a suitable platform for the development of new anticancer therapeutics. (C) 2014 Elsevier Ltd. All rights reserved.