1,3-diallylpyrimidine-2,4,6(1H,3H,5H)-trione | 46388-65-2

• 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-diallylpyrimidine-2,4,6(1H,3H,5H)-trione
• 英文别名: diallylbarbituric acid；Barbituric acid, 1,3-diallyl-；1,3-bis(prop-2-enyl)-1,3-diazinane-2,4,6-trione
• CAS: 46388-65-2
• 化学式: C₁₀H₁₂N₂O₃
• 分子量: 208.217
• InChiKey: AHWOMRLECMJDLU-UHFFFAOYSA-N

物化性质

• 沸点：
  296.6±43.0 °C(Predicted)
• 密度：
  1.180±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,3-diallylpyrimidine-2,4,6(1H,3H,5H)-trione 在 溶剂黄146 、 锌 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 5-benzyl-1,3-diallylpyrimidine-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
• 作为产物：
  描述：

  丙二酸 、 1,3-二烯丙基脲 在 乙酸酐 作用下， 反应 0.17h， 以95%的产率得到1,3-diallylpyrimidine-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

• [EN] FUSED PYRIMIDINE-DIONE DERIVATIVES AS TRPA1 MODULATORS<br/>[FR] DÉRIVÉS DE PYRIMIDINEDIONES FUSIONNÉS UTILISÉS COMME MODULATEURS DES RÉCEPTEURS TRPA1
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2010109287A1

  公开（公告）日：2010-09-30

  The invention described herein relates to novel fused pyrimidinediones derivatives of formula (I) which are TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPAl (Transient Receptor Potential subfamily A, member 1). This invention also provides processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPAl. Formula (I)

  本发明描述的是一类新颖的杂合吡啶二酮衍生物，其化学公式为（I），这些衍生物是TRPA（瞬时受体电位亚家族A）的调节剂。特别是，本文所述的化合物对于治疗或预防由TRPA1（瞬时受体电位亚家族A成员1）调控的疾病、状况和/或失调是有用的。本发明还提供了制备所述化合物、它们合成中使用的中间体、药物组合物以及治疗或预防由TRPA1调控的疾病、状况和/或失调的方法。公式（I）
• Pilot Plant Preparation of an α_vβ₃ Integrin Antagonist. Part 1. Process Research and Development of a (<i>S</i>)-β-Amino Acid Ester Intermediate:  Synthesis via a Scalable, Diastereoselective Imino-Reformatsky Reaction
  作者：Jerry D. Clark、Gerald A. Weisenburger、D. Keith Anderson、Pierre-Jean Colson、Albert D. Edney、Donald J. Gallagher、H. Peter Kleine、Carl M. Knable、Melissa K. Lantz、Christine M. V. Moore、James B. Murphy、Thomas E. Rogers、Peter G. Ruminski、Ajit S. Shah、Neil Storer、Bruce E. Wise

  DOI：10.1021/op034094j

  日期：2004.1.1

  enantioselective method for preparing (S)-β-amino acid ester 3, a key intermediate to the αvβ3 integrin antagonist 1. Reported are an asymmetric Michael reaction approach, attempts to enantioselectively hydrogenate an enamine, resolution of (±)-3 via diastereomeric salt formation, and a synthetic route employing a novel, diastereoselective imino-Reformatsky reaction. This last research initiative proved

  描述了四项过程研究调查，旨在辨别制备 (S)-β-氨基酸酯 3（αvβ3 整合素拮抗剂 1 的关键中间体）的可扩展的对映选择性方法。报告的是不对称迈克尔反应方法，试图对映选择性氢化烯胺，通过非对映体盐的形成拆分 (±)-3，以及采用新型非对映选择性亚氨基-Reformatsky 反应的合成路线。最后一项研究计划被证明是成功的，并被用作初始 API 供应的促成途径。报道了这种使能化学的工艺开发。研究和优化的技术问题是（1）在亚氨基-Reformatsky反应中采用MEM保护以获得高产率和非对映选择性的必要性，
• [EN] AMIDES OF HETEROCYCLIC COMPOUNDS AS TRPA1 INHIBITORS<br/>[FR] AMIDES DE COMPOSÉS HÉTÉROCYCLIQUES À TITRE D'INHIBITEURS DE TRPA1
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2011114184A1

  公开（公告）日：2011-09-22

  Amides of heterocyclic compounds as Transient Receptor Potential subfamily A (TRPA) modulators are provided In particular, compounds described herein are useful for treating or preventing diseases, conditions and/ or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1) Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1. (I).

  提供了杂环化合物的酰胺作为瞬时受体电位亚家族A（TRPA）调节剂。具体来说，本文描述的化合物可用于治疗或预防由TRPA1（瞬时受体电位亚家族A，成员1）调节的疾病、症状和/或疾病。本文还提供了制备本文描述的化合物的方法、其合成中使用的中间体、药物组合物以及治疗或预防由TRPA1调节的疾病、症状和/或疾病的方法。
• FUSED PYRIMIDINE-DIONE DERIVATIVES AS TRPAI MODULATORS
  申请人：Chaudhari Sachin Sundarlal

  公开号：US20120041004A1

  公开（公告）日：2012-02-16

  The invention described herein relates to novel fused pyrimidinediones derivatives of formula (I) which are TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1). This invention also provides processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1.

  本发明涉及化合物公式(I)的新型融合嘧啶二酮衍生物，其为TRPA（瞬时受体电位亚家族A）调节剂。特别地，本发明所描述的化合物可用于治疗或预防由TRPA1（瞬时受体电位亚家族A，成员1）调节的疾病、状况和/或障碍。本发明还提供了制备所述化合物的方法、用于其合成的中间体、其制药组合物以及用于治疗或预防由TRPA1调节的疾病、状况和/或障碍的方法。
• FUROPYRIMIDINEDIONE DERIVATIVES AS TRPAI MODULATORS
  申请人：Chaudhari Sachin Sundarlal

  公开号：US20120178766A1

  公开（公告）日：2012-07-12

  The present invention is related to novel furopyrimidinedione derivatives as TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPA1 (Transient Receptor Potential subfamily A, member 1). Also provided herein are processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPA1.

  本发明涉及新型噻吩嘧啶二酮衍生物作为TRPA（瞬时受体电位亚家族A）调节剂。特别地，本文所描述的化合物可用于治疗或预防由TRPA1（瞬时受体电位亚家族A，成员1）调节的疾病、情况和/或疾患。本文还提供了用于制备所述化合物的过程，用于其合成的中间体，其制药组合物以及用于治疗或预防由TRPA1调节的疾病、情况和/或疾患的方法。