6-chloro-1-phenylpyrimidine-2,4(1H,3H)-dione | 155700-29-1

• 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: 6-chloro-1-phenylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 6-chloro-1-phenyluracil；6-Chloro-1-phenylpyrimidine-2,4-dione
• CAS: 155700-29-1
• 化学式: C₁₀H₇ClN₂O₂
• 分子量: 222.631
• InChiKey: HGSAMYRSXJOFCZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-chloro-1-phenylpyrimidine-2,4(1H,3H)-dione 在 ammonium hydroxide 、 锌 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以75%的产率得到1-苯基尿嘧啶
  参考文献：
  名称：

  Isolation of New Chlorinated Regioisomers of Mono N-Substituted Uracil Derivatives and Synthesis of 3-Substituted 8-Phenylpyrimido[5,4-e]-1,2,4-triazine-5,7(6H,8H)-diones

  摘要：

  A variety of fervenulin type products, 3-substituted 8-phenylpyrimido[5,4-e]-1,2,4-triazine-5,7(6H,8H)-diones (18a-i), were synthesized by nitrosative or nitrative cyclization of the aldehyde hydrazones (17a-i) derived from 6-(1-methylhydrazino)-1-phenyluracil (16) with aliphatic as well as aromatic aldehydes. The compound (16) was prepared by the reaction of 6-chloro-1-phenyluracil (8) with methylhydrazine. In addition, not only the precursor of 16, 6-chloro-1-phenyluracil (8), but also other new chlorinated regioisomers of mono N-substituted pyrimidine (9) and uracil (14) were isolated and characterized by the reductive dechlorination of them.

  DOI：

  10.3987/com-93-s146
• 作为产物：
  描述：

  N-苯基巴比土酸 在 三氯氧磷 作用下， 以 水 为溶剂， 反应 3.0h， 以48%的产率得到6-chloro-1-phenylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Investigation of 3-aryl-pyrimido[5,4-e][1,2,4]triazine-5,7-diones as small molecule antagonists of β-catenin/TCF transcription

  摘要：

  Nearly all colorectal cancers (CRCs) and varied subsets of other cancers have somatic mutations leading to beta-catenin stabilization and increased beta-catenin/TCF transcriptional activity. Inhibition of stabilized beta-catenin in CRC cell lines arrests their growth and highlights the potential of this mechanism for novel cancer therapeutics. We have pursued efforts to develop small molecules that inhibit beta-catenin/TCF transcriptional activity. We used xanthothricin, a known beta-catenin/TCF antagonist of microbial origin, as a lead compound to synthesize related analogues with drug-like features such as low molecular weight and good metabolic stability. We studied a panel of six candidate Wnt/beta-catenin/Tcf-regulated genes and found that two of them (Axin2, Lgr5) were reproducibly activated (9-10 fold) in rat intestinal epithelial cells (IEC-6) following beta-catenin stabilization by Wnt-3a ligand treatment. Two previously reported beta-catenin/TCF antagonists (calphostin C, xanthothricin) and XAV939 (tankyrase antagonist) inhibited Wnt-activated genes in a dose-dependent fashion. We found that four of our compounds also potently inhibited Wnt-mediated activation in the panel of target genes. We investigated the mechanism of action for one of these (8c) and demonstrated these novel small molecules inhibit beta-catenin transcriptional activity by degrading beta-catenin via a proteasome-dependent, but GSK3 beta-, APC-, AXIN2- and beta TrCP-independent, pathway. The data indicate the compounds act at the level of beta-catenin to inhibit Wnt/beta-catenin/TCF function and highlight a robust strategy for assessing the activity of beta-catenin/TCF antagonists. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.111

文献信息

• US3957786A
  申请人：——

  公开号：US3957786A

  公开（公告）日：1976-05-18
• US4067982A
  申请人：——

  公开号：US4067982A

  公开（公告）日：1978-01-10
• Investigation of 3-aryl-pyrimido[5,4-e][1,2,4]triazine-5,7-diones as small molecule antagonists of β-catenin/TCF transcription
  作者：Jörg Zeller、Anjanette J. Turbiak、Ian A. Powelson、Surin Lee、Duxin Sun、H.D. Hollis Showalter、Eric R. Fearon

  DOI：10.1016/j.bmcl.2013.08.111

  日期：2013.11

  Nearly all colorectal cancers (CRCs) and varied subsets of other cancers have somatic mutations leading to beta-catenin stabilization and increased beta-catenin/TCF transcriptional activity. Inhibition of stabilized beta-catenin in CRC cell lines arrests their growth and highlights the potential of this mechanism for novel cancer therapeutics. We have pursued efforts to develop small molecules that inhibit beta-catenin/TCF transcriptional activity. We used xanthothricin, a known beta-catenin/TCF antagonist of microbial origin, as a lead compound to synthesize related analogues with drug-like features such as low molecular weight and good metabolic stability. We studied a panel of six candidate Wnt/beta-catenin/Tcf-regulated genes and found that two of them (Axin2, Lgr5) were reproducibly activated (9-10 fold) in rat intestinal epithelial cells (IEC-6) following beta-catenin stabilization by Wnt-3a ligand treatment. Two previously reported beta-catenin/TCF antagonists (calphostin C, xanthothricin) and XAV939 (tankyrase antagonist) inhibited Wnt-activated genes in a dose-dependent fashion. We found that four of our compounds also potently inhibited Wnt-mediated activation in the panel of target genes. We investigated the mechanism of action for one of these (8c) and demonstrated these novel small molecules inhibit beta-catenin transcriptional activity by degrading beta-catenin via a proteasome-dependent, but GSK3 beta-, APC-, AXIN2- and beta TrCP-independent, pathway. The data indicate the compounds act at the level of beta-catenin to inhibit Wnt/beta-catenin/TCF function and highlight a robust strategy for assessing the activity of beta-catenin/TCF antagonists. (c) 2013 Elsevier Ltd. All rights reserved.
• Isolation of New Chlorinated Regioisomers of Mono N-Substituted Uracil Derivatives and Synthesis of 3-Substituted 8-Phenylpyrimido[5,4-e]-1,2,4-triazine-5,7(6H,8H)-diones
  作者：Tomohisa Nagamatsu、Hirofumi Yamasaki、Fumio Yoneda

  DOI：10.3987/com-93-s146

  日期：——

  A variety of fervenulin type products, 3-substituted 8-phenylpyrimido[5,4-e]-1,2,4-triazine-5,7(6H,8H)-diones (18a-i), were synthesized by nitrosative or nitrative cyclization of the aldehyde hydrazones (17a-i) derived from 6-(1-methylhydrazino)-1-phenyluracil (16) with aliphatic as well as aromatic aldehydes. The compound (16) was prepared by the reaction of 6-chloro-1-phenyluracil (8) with methylhydrazine. In addition, not only the precursor of 16, 6-chloro-1-phenyluracil (8), but also other new chlorinated regioisomers of mono N-substituted pyrimidine (9) and uracil (14) were isolated and characterized by the reductive dechlorination of them.