N1,N2-dimethyl-N1-((3-(4-(3-(2-(tetrahydro-2H-pyran-4-yl)ethoxy)cyclobutoxy)phenyl)-1H-pyrazol-4-yl)methyl)ethane-1,2-diamine bis(2,2,2-trifluoroacetate)

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N1,N2-dimethyl-N1-((3-(4-(3-(2-(tetrahydro-2H-pyran-4-yl)ethoxy)cyclobutoxy)phenyl)-1H-pyrazol-4-yl)methyl)ethane-1,2-diamine bis(2,2,2-trifluoroacetate)
• 英文别名: EPZ020411；Epz020411；N,N'-dimethyl-N'-[[5-[4-[3-[2-(oxan-4-yl)ethoxy]cyclobutyl]oxyphenyl]-1H-pyrazol-4-yl]methyl]ethane-1,2-diamine
• 化学式: C₂₅H₃₈N₄O₃
• 分子量: 442.602
• InChiKey: QMDKVNSQXPVCRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  71.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl methyl(2-(methyl((1-(tetrahydro-2H-pyran-2-yl)-3-(4-(3-(2-(tetrahydro-2H-pyran-4-yl)ethoxy)cyclobutoxy)phenyl)-1H-pyrazol-4-yl)methyl)amino)ethyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以41%的产率得到N1,N2-dimethyl-N1-((3-(4-(3-(2-(tetrahydro-2H-pyran-4-yl)ethoxy)cyclobutoxy)phenyl)-1H-pyrazol-4-yl)methyl)ethane-1,2-diamine bis(2,2,2-trifluoroacetate)
  参考文献：
  名称：

  Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound

  摘要：

  A novel aryl pyrazole series of arginine methyltransferase inhibitors has been identified. Synthesis of analogues within this series yielded the first potent, selective, small molecule PRMT6 inhibitor tool compound, EPZ020411. PRMT6 overexpression has been reported in several cancer types suggesting that inhibition of PRMT6 activity may have therapeutic utility. Identification of EPZ020411 provides the field with the first small molecule tool compound for target validation studies. EPZ020411 shows good bioavailability following subcutaneous dosing in rats making it a suitable tool for in vivo studies.

  DOI：

  10.1021/acsmedchemlett.5b00071

文献信息

• ARGININE METHYLTRANSFERASE INHIBITORS AND USES THEREOF
  申请人：Epizyme, Inc.

  公开号：US20170283400A1

  公开（公告）日：2017-10-05

  Provided herein are various compounds, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.
• INHIBITION OF DIPEPTIDE REPEAT PROTEINS
  申请人：ALS Therapy Development Institute

  公开号：US20200405689A1

  公开（公告）日：2020-12-31

  Methods are disclosed for treating neurodegenerative disorders, such as ALS and FTD by using an effective amount of a type I protein arginine methyltransferase (Type I PRMT) inhibitor to decrease cellular toxicity caused by dipeptide repeat proteins (DRPs).
• Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound
  作者：Lorna H. Mitchell、Allison E. Drew、Scott A. Ribich、Nathalie Rioux、Kerren K. Swinger、Suzanne L. Jacques、Trupti Lingaraj、P. Ann Boriack-Sjodin、Nigel J. Waters、Tim J. Wigle、Oscar Moradei、Lei Jin、Tom Riera、Margaret Porter-Scott、Mikel P. Moyer、Jesse J. Smith、Richard Chesworth、Robert A. Copeland

  DOI：10.1021/acsmedchemlett.5b00071

  日期：2015.6.11

  A novel aryl pyrazole series of arginine methyltransferase inhibitors has been identified. Synthesis of analogues within this series yielded the first potent, selective, small molecule PRMT6 inhibitor tool compound, EPZ020411. PRMT6 overexpression has been reported in several cancer types suggesting that inhibition of PRMT6 activity may have therapeutic utility. Identification of EPZ020411 provides the field with the first small molecule tool compound for target validation studies. EPZ020411 shows good bioavailability following subcutaneous dosing in rats making it a suitable tool for in vivo studies.