N-benzyl-1-octyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide | 1099823-24-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-benzyl-1-octyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
• 英文别名: N-benzyl-1-octyl-5-uracilcarboxamide；N-benzyl-1-octyl-2,4-dioxopyrimidine-5-carboxamide
• CAS: 1099823-24-1
• 化学式: C₂₀H₂₇N₃O₃
• 分子量: 357.453
• InChiKey: PAZQDBILEOAHMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  78.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-溴辛烷 在 2,6-二甲基吡啶 、 dipotassium peroxodisulfate 、 sodium hydride 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 copper(II) sulfate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 29.5h， 生成 N-benzyl-1-octyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
  参考文献：
  名称：

  C(5) modified uracil derivatives showing antiproliferative and erythroid differentiation inducing activities on human chronic myelogenous leukemia K562 cells

  摘要：

  The K562 cell line has been proposed as a useful experimental system to identify anti-tumor compounds acting by inducing terminal erythroid differentiation. K562 cells exhibit a low proportion of hemoglobin-synthesizing cells under standard cell growth conditions, but are able to undergo terminal erythroid differentiation when treated with a variety of anti-tumor compounds. In this paper we report a screening study on a set of different modified C(5) uracil derivatives for the evaluation of their antiproliferative effect in connection with erythroid differentiation pathways, and for defining a new class of drug candidates for the treatment of chronic myelogenous leukemia. Activity of the derivatives tested can be classified in two effect: an antiproliferative effect linked to a high level of erythroid differentiation activity and an antiproliferative effect without activation of gamma globin genes The highest antiproliferative effect and erythroid induction was shown by compound 9, a thymine derivative bearing a n-octyl chain on nitrogen N(1), whereas thymine did not show any effect, suggesting the importance of the linear alkyl chain in position N(1). To our knowledge this compound should be considered among the most efficient inducers of erythroid differentiation of K562 cells. This work is the starting point for the quest of more effective and specific drugs for the induction of terminal erythroid differentiation, for leading new insights in the treatment of neoplastic diseases with molecules acting by inducing differentiation rather than by simply exerting cytotoxic effects. (C) 2011 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejphar.2011.09.024

文献信息

• New Uracil Dimers Showing Erythroid Differentiation Inducing Activities
  作者：Alessandro Accetta、Roberto Corradini、Stefano Sforza、Tullia Tedeschi、Eleonora Brognara、Monica Borgatti、Roberto Gambari、Rosangela Marchelli

  DOI：10.1021/jm800982q

  日期：2009.1.8

  The synthesis of C5 linked uracil dimers was carried out according to a model developed in order to bind adenine in DNA. NI-Alkylated uracil derivatives were synthesized from isoorotic acid (uracil-5-carboxylic acid) or thymine. The carboxylic acid derivatives were condensed with diamines in order to produce dimeric compounds or with monoamines in order to obtain reference monomeric compounds. Some of the derivatives, in particular the uracil dimers, showed antiproliferative and erythroid differentiation induction properties towards human chronic myelogenous leukemia K562 cells, thus indicating that these compounds could represent a new class of drugs useful for the development of antitumor therapy based on the ability to induce terminal differentiation.
• C(5) modified uracil derivatives showing antiproliferative and erythroid differentiation inducing activities on human chronic myelogenous leukemia K562 cells
  作者：Eleonora Brognara、Ilaria Lampronti、Giulia Breveglieri、Alessandro Accetta、Roberto Corradini、Alex Manicardi、Monica Borgatti、Alessandro Canella、Chiara Multineddu、Rosangela Marchelli、Roberto Gambari

  DOI：10.1016/j.ejphar.2011.09.024

  日期：2011.12

  The K562 cell line has been proposed as a useful experimental system to identify anti-tumor compounds acting by inducing terminal erythroid differentiation. K562 cells exhibit a low proportion of hemoglobin-synthesizing cells under standard cell growth conditions, but are able to undergo terminal erythroid differentiation when treated with a variety of anti-tumor compounds. In this paper we report a screening study on a set of different modified C(5) uracil derivatives for the evaluation of their antiproliferative effect in connection with erythroid differentiation pathways, and for defining a new class of drug candidates for the treatment of chronic myelogenous leukemia. Activity of the derivatives tested can be classified in two effect: an antiproliferative effect linked to a high level of erythroid differentiation activity and an antiproliferative effect without activation of gamma globin genes The highest antiproliferative effect and erythroid induction was shown by compound 9, a thymine derivative bearing a n-octyl chain on nitrogen N(1), whereas thymine did not show any effect, suggesting the importance of the linear alkyl chain in position N(1). To our knowledge this compound should be considered among the most efficient inducers of erythroid differentiation of K562 cells. This work is the starting point for the quest of more effective and specific drugs for the induction of terminal erythroid differentiation, for leading new insights in the treatment of neoplastic diseases with molecules acting by inducing differentiation rather than by simply exerting cytotoxic effects. (C) 2011 Elsevier B.V. All rights reserved.