1,3-dibenzyl-5-(2,6-dimethyl-4-hydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione

• 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: 1,3-dibenzyl-5-(2,6-dimethyl-4-hydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
• 英文别名: EML425；1,3-Dibenzyl-5-(4-hydroxy-2,6-dimethylbenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione；1,3-dibenzyl-5-[(4-hydroxy-2,6-dimethylphenyl)methylidene]-1,3-diazinane-2,4,6-trione
• 化学式: C₂₇H₂₄N₂O₄
• 分子量: 440.499
• InChiKey: LUGQBJDYUPNAQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  77.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,3-二苄基脲 在 乙酸酐 作用下， 以 乙醇 为溶剂， 反应 1.17h， 生成 1,3-dibenzyl-5-(2,6-dimethyl-4-hydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
  参考文献：
  名称：

  A Novel Cell-Permeable, Selective, and Noncompetitive Inhibitor of KAT3 Histone Acetyltransferases from a Combined Molecular Pruning/Classical Isosterism Approach

  摘要：

  Selective inhibitors of the two paralogue KAT3 acetyltransferases (CBP and p300) may serve not only as precious chemical tools to investigate the role of these enzymes in physiopathological mechanisms but also as lead structures for the development of further antitumor agents. After the application of a molecular pruning approach to the hardly optimizable and not very cell-permeable garcinol core structure, we prepared many analogues that were screened for their inhibitory effects using biochemical and biophysical (SPR) assays. Further optimization led to the discovery of the benzylidenebarbituric acid derivative 7h (EML425) as a potent and selective reversible inhibitor of CBP/p300, noncompetitive versus both acetyl-CoA and a histone H3 peptide, and endowed with good cell permeability. Furthermore, in human leukemia U937 cells, it induced a marked and time-dependent reduction in the acetylation of lysine H4K5 and H3K9, a marked arrest in the G0/G1 phase and a significant increase in the hypodiploid nuclei percentage.

  DOI：

  10.1021/jm5019687

文献信息

• HETEROCYCLIC COMPOUNDS AND USES THEREOF
  申请人：Plexxikon Inc.

  公开号：US20170081326A1

  公开（公告）日：2017-03-23

  Provided herein are heterocyclic compounds of Formula (I), pharmaceutical compositions containing such a compound and their therapeutic uses, methods for their preparation, intermediate compounds, pharmaceutical compositions containing such a compound, and their therapeutic uses.

  本文提供的是公式（I）的杂环化合物，包括含有该化合物的药物组合物及其治疗用途，制备方法，中间体化合物，含有该化合物的药物组合物以及其治疗用途。
• Heterocyclic compounds and uses thereof
  申请人：Plexxikon Inc.

  公开号：US10370374B2

  公开（公告）日：2019-08-06

  Provided herein are heterocyclic compounds of Formula (I), pharmaceutical compositions containing such a compound and their therapeutic uses, methods for their preparation, intermediate compounds, pharmaceutical compositions containing such a compound, and their therapeutic uses.

  本文提供了式（I）杂环化合物、含有此类化合物的药物组合物及其治疗用途、其制备方法、中间体化合物、含有此类化合物的药物组合物及其治疗用途。
• Crystalline forms of a compound that inhibits bromodomain
  申请人：Plexxikon Inc.

  公开号：US10577366B2

  公开（公告）日：2020-03-03

  Forms of 4-(1-(1,1-di(pyridin-2-yl)ethyl)-6-(3,5-dimethylisoxazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the forms of Compound I.

  制备了 4-(1-(1,1-二(吡啶-2-基)乙基)-6-(3,5-二甲基异恶唑-4-基)-1H-吡咯并[3,2-b]吡啶-3-基)苯甲酸的固态形式，并对其进行了表征： 还提供了化合物 I 的制造工艺和使用方法。
• Solid forms of a compound for modulating kinases
  申请人：Plexxikon Inc.

  公开号：US10717735B2

  公开（公告）日：2020-07-21

  Forms of 4-(6-(3,5-dimethylisoxazol-4-yl)-1-[(1S)-1-(2-pyridyl)ethyl]pyrrolo[3,2-b]pyridin-3-yl)benzoic acid (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the forms of Compound I.

  制备了 4-(6-(3,5-二甲基异恶唑-4-基)-1-[(1S)-1-(2-吡啶基)乙基]吡咯并[3,2-b]吡啶-3-基)苯甲酸（化合物 I）的固态形式，并对其进行了表征： 此外，还提供了化合物 I 的制造工艺和使用方法。
• CRYSTALLINE FORMS OF 4-(1-(1,1-DI(PYRIDIN-2-YL)ETHYL)-6-(3,5-DIMETHYLISOXAZOL-4-YL)-1H-
PYRROLO[3,2-B]PYRIDIN-3-YL)BENZOIC ACID THAT INHIBITS BROMODOMAIN
  申请人：Plexxikon Inc.

  公开号：EP3601281B1

  公开（公告）日：2021-09-29