(E)-4-(3-(pyridin-4-yl)triaz-1-enyl)benzimidamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (E)-4-(3-(pyridin-4-yl)triaz-1-enyl)benzimidamide
• 英文别名: 4-(2-Pyridin-4-yliminohydrazinyl)benzenecarboximidamide；4-(2-pyridin-4-yliminohydrazinyl)benzenecarboximidamide
• 化学式: C₁₂H₁₂N₆
• 分子量: 240.267
• InChiKey: KIWVECKMAJTTBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氨基吡啶 、 4-aminobenzamidine dihydrochloride 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 0.5h， 以51%的产率得到(E)-4-(3-(pyridin-4-yl)triaz-1-enyl)benzimidamide
  参考文献：
  名称：

  Alkyne-substituted diminazene as G-quadruplex binders with anticancer activities

  摘要：

  G-quadruplex ligands have been touted as potential anticancer agents, however, none of the reported G-quadruplex-interactive small molecules have gone past phase II clinical trials. Recently it was revealed that diminazene (berenil, DMZ) actually binds to G-quadruplexes 1000 times better than DNA duplexes, with dissociation constants approaching 1 nM. DMZ however does not have strong anticancer activities. In this paper, using a panel of biophysical tools, including NMR, FRET melting assay and FRET competition assay, we discovered that monoamidine analogues of DMZ bearing alkyne substitutes selectively bind to G-quadruplexes. The lead DMZ analogues were shown to be able to target c-MYC G-quadruplex both in vitro and in vivo. Alkyne DMZ analogues display respectable anticancer activities (single digit micromolar GI(50)) against ovarian (OVCAR-3), prostate (PC-3) and triple negative breast (MDA-MB-231) cancer cell lines and represent interesting new leads to develop anticancer agents. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.030

文献信息

• Alkyne-substituted diminazene as G-quadruplex binders with anticancer activities
  作者：Changhao Wang、Brandon Carter-Cooper、Yixuan Du、Jie Zhou、Musabbir A. Saeed、Jinbing Liu、Min Guo、Benjamin Roembke、Clinton Mikek、Edwin A. Lewis、Rena G. Lapidus、Herman O. Sintim

  DOI：10.1016/j.ejmech.2016.04.030

  日期：2016.8

  G-quadruplex ligands have been touted as potential anticancer agents, however, none of the reported G-quadruplex-interactive small molecules have gone past phase II clinical trials. Recently it was revealed that diminazene (berenil, DMZ) actually binds to G-quadruplexes 1000 times better than DNA duplexes, with dissociation constants approaching 1 nM. DMZ however does not have strong anticancer activities. In this paper, using a panel of biophysical tools, including NMR, FRET melting assay and FRET competition assay, we discovered that monoamidine analogues of DMZ bearing alkyne substitutes selectively bind to G-quadruplexes. The lead DMZ analogues were shown to be able to target c-MYC G-quadruplex both in vitro and in vivo. Alkyne DMZ analogues display respectable anticancer activities (single digit micromolar GI(50)) against ovarian (OVCAR-3), prostate (PC-3) and triple negative breast (MDA-MB-231) cancer cell lines and represent interesting new leads to develop anticancer agents. (C) 2016 Elsevier Masson SAS. All rights reserved.