6-(4-Biphenylyl)-4(3H)-oxopyrimidine-2-thiol

• 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: 6-(4-Biphenylyl)-4(3H)-oxopyrimidine-2-thiol
• 英文别名: 6-(4-Biphenylyl)-4(3H)-oxopyrimidin-2-thiol；6-(4-phenylphenyl)-2-sulfanylidene-1H-pyrimidin-4-one
• 化学式: C₁₆H₁₂N₂OS
• 分子量: 280.35
• InChiKey: AMNLXNKKHDPYQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(4-Biphenylyl)-4(3H)-oxopyrimidine-2-thiol 在 potassium carbonate 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成
  参考文献：
  名称：

  Identification of novel quinazoline derivatives as potent antiplasmodial agents

  摘要：

  Despite the recent reductions in the global burden of malaria, this disease remains a devastating cause of death in tropical and subtropical regions. As there is no broadly effective vaccine for malaria, prevention and treatment still rely on chemotherapy. Unfortunately, emerging resistance to the gold standard artemisinin combination therapies means that new drugs with novel modes of action are urgently needed. In this context, Plasmodium histone modifying enzymes have emerged as potential drug targets, prompting us to develop and optimize compounds directed against such epigenetic targets. A panel of 51 compounds designed to target different epigenetic enzymes were screened for activity against Plasmodium falciparum parasites. Based on in vitro activity against drug susceptible and drug-resistant P. falciparum lines, selectivity index criterion and favorable pharmacokinetic properties, four compounds, one HDAC inhibitor (1) and three DNMT inhibitors (37,43 and 45), were selected for preclinical studies in a mouse model of malaria. In vivo data showed that 37, 43 and 45 exhibited oral efficacy in the mouse model of Plasmodium berghei infection. These compounds represent promising starting points for the development of novel antimalarial drugs. Crown Copyright (C) 2018 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.10.041
• 作为产物：
  描述：

  硫脲 、 3-联苯-3-氧丙酸乙酯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 生成 6-(4-Biphenylyl)-4(3H)-oxopyrimidine-2-thiol
  参考文献：
  名称：

  Novel uracil-based 2-aminoanilide and 2-aminoanilide-like derivatives: Histone deacetylase inhibition and in-cell activities

  摘要：

  A novel series of non-hydroxamate HDAC inhibitors (HDACi) showing a uracil group at the left and a 2-aminoanilide/2-aminoanilide- like portion at the right head have been reported. In particular, the new compounds incorporating a 2-aminoanilide moiety behaved as class I-selective HDACi. Compound 8, the most potent and class I-selective, showed weak apoptosis (higher than MS-275) joined to cytodifferentiating activity on U937 cells. Surprisingly, the highest differentiation was observed with 13, through an effect that seems to be unrelated to HDAC inhibition. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.03.055

文献信息

• COMPOUNDS USEFUL AS AICARFT INHIBITORS
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1109560B1

  公开（公告）日：2003-08-27
• EP1109560A4
  申请人：——

  公开号：EP1109560A4

  公开（公告）日：2002-04-17
• US6525050B1
  申请人：——

  公开号：US6525050B1

  公开（公告）日：2003-02-25
• [EN] COMPOUNDS USEFUL AS AICARFT INHIBITORS<br/>[FR] COMPOSES UTILES EN TANT QU'INHIBITEURS D'AICARFT
  申请人：AGOURON PHARMA

  公开号：WO2000013688A1

  公开（公告）日：2000-03-16

  Coumpounds of the formula (I) (where R?1, R2, and R3¿ are as defined in the specification) are inhibitors of AICARFT. These compounds, as well as their pharmaceutically acceptable salts, solvates, prodrugs, and pharmaceutically active metabolites, are useful in pharmaceutical compositions for treating diseases such as cancer.
• Novel uracil-based 2-aminoanilide and 2-aminoanilide-like derivatives: Histone deacetylase inhibition and in-cell activities
  作者：Antonello Mai、Andrea Perrone、Angela Nebbioso、Dante Rotili、Sergio Valente、Maria Tardugno、Silvio Massa、Floriana De Bellis、Lucia Altucci

  DOI：10.1016/j.bmcl.2008.03.055

  日期：2008.4

  A novel series of non-hydroxamate HDAC inhibitors (HDACi) showing a uracil group at the left and a 2-aminoanilide/2-aminoanilide- like portion at the right head have been reported. In particular, the new compounds incorporating a 2-aminoanilide moiety behaved as class I-selective HDACi. Compound 8, the most potent and class I-selective, showed weak apoptosis (higher than MS-275) joined to cytodifferentiating activity on U937 cells. Surprisingly, the highest differentiation was observed with 13, through an effect that seems to be unrelated to HDAC inhibition. (c) 2008 Elsevier Ltd. All rights reserved.