1-(2-amino-4-methyl-6-(methylthio)pyrimidin-5-yl)ethanone | 202467-77-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 1-(2-amino-4-methyl-6-(methylthio)pyrimidin-5-yl)ethanone
• 英文别名: 1-(2-amino-4-methyl-6-(methylthio)pyrimidin-5-yl)ethan-1-one；5-Acetyl-2-amino-6-methyl-4-methylthiopyrimidine；1-(2-amino-4-methyl-6-methylsulfanylpyrimidin-5-yl)ethanone
• CAS: 202467-77-4
• 化学式: C₈H₁₁N₃OS
• 分子量: 197.261
• InChiKey: KUEOXZREMJPMCQ-UHFFFAOYSA-N

物化性质

• 沸点：
  399.7±52.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-amino-4-methyl-6-(methylthio)pyrimidin-5-yl)ethanone 在 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 1-((6-bromobenzo[d][1,3]dioxol-5-yl)methyl)-3,4-dimethyl-1H-pyrazolo[3,4-d]pyrimidin-6-amine
  参考文献：
  名称：

  Development of pyrazolo[3,4-d]pyrimidine-6-amine-based TRAP1 inhibitors that demonstrate in vivo anticancer activity in mouse xenograft models

  摘要：

  TNF Receptor Associated Protein 1 (TRAP1) is a mitochondrial paralog of Hsp90 related to the promotion of tumorigenesis in various cancers via maintaining mitochondrial integrity, reducing the production of reactive oxygen species, and reprogramming cellular metabolism. Consequently, Hsp90 and TRAP1 have been targeted to develop cancer therapeutics. Herein, we report a series of pyrazolo[3,4-d]pyrimidine derivatives that are mi-tochondria-permeable TRAP1 inhibitors. Structure-based drug design guided the optimization of potency, leading to the identification of compounds 47 and 48 as potent TRAP1 and Hsp90 inhibitors with good meta-bolic and plasma stability as well as acceptable CYP and hERG inhibition. X-ray co-crystallization studies con-firmed both 47 and 48 interact with the ATP binding pocket in the TRAP1 protein. Compounds 47 and 48 demonstrated excellent anticancer efficiency in various cancer cells, with limited toxicity over normal hepato-cyte and prostate cells. Mouse PC3 xenograft studies showed 47 and 48 significantly reduced tumor growth.

  DOI：

  10.1016/j.bioorg.2020.103901
• 作为产物：
  描述：

  diacetylketene N,S-acetal 在 sodium methylate 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 3.5h， 生成 1-(2-amino-4-methyl-6-(methylthio)pyrimidin-5-yl)ethanone
  参考文献：
  名称：

  Heterocyclization of acetylketeneN,S-acetals with benzoyl cyanamide

  摘要：

  N-Unsubstituted mono-and diacetylketene N,S-acetals undergo cyclization with benzoyl cyanamide to form 2-amino-4-methylthiopyrimidine derivatives.

  DOI：

  10.1007/bf02503799

文献信息

• Microwave-Assisted Solvent-Free Synthesis of Highly Functionalized Pyrimidine Derivatives
  作者：Shengjiao Yan、Yanfei Niu、Xuebing Chen、Yongjiang Liu、Jun Lin

  DOI：10.1002/jhet.891

  日期：2012.7

  We here described an efficient method for the synthesis of a series of highly functionalized pyrimidines via the addition and condensation reaction of ketene dithioacetals with guanidine carbonate or amidine hydrochlorides by microwave irradiation under solvent‐free conditions in the absence of a catalyst, giving the products with good yields (79–98%).
• Heterocyclization of acetylketeneN,S-acetals with benzoyl cyanamide
  作者：V. A. Dorokhov、A. V. Komkov、V. S. Bogdanov

  DOI：10.1007/bf02503799

  日期：1997.11

  N-Unsubstituted mono-and diacetylketene N,S-acetals undergo cyclization with benzoyl cyanamide to form 2-amino-4-methylthiopyrimidine derivatives.
• Development of pyrazolo[3,4-d]pyrimidine-6-amine-based TRAP1 inhibitors that demonstrate in vivo anticancer activity in mouse xenograft models
  作者：Darong Kim、So-Yeon Kim、Dongyoung Kim、Nam Gu Yoon、Jisu Yun、Ki Bum Hong、Changwook Lee、Ji Hoon Lee、Byoung Heon Kang、Soosung Kang

  DOI：10.1016/j.bioorg.2020.103901

  日期：2020.8

  TNF Receptor Associated Protein 1 (TRAP1) is a mitochondrial paralog of Hsp90 related to the promotion of tumorigenesis in various cancers via maintaining mitochondrial integrity, reducing the production of reactive oxygen species, and reprogramming cellular metabolism. Consequently, Hsp90 and TRAP1 have been targeted to develop cancer therapeutics. Herein, we report a series of pyrazolo[3,4-d]pyrimidine derivatives that are mi-tochondria-permeable TRAP1 inhibitors. Structure-based drug design guided the optimization of potency, leading to the identification of compounds 47 and 48 as potent TRAP1 and Hsp90 inhibitors with good meta-bolic and plasma stability as well as acceptable CYP and hERG inhibition. X-ray co-crystallization studies con-firmed both 47 and 48 interact with the ATP binding pocket in the TRAP1 protein. Compounds 47 and 48 demonstrated excellent anticancer efficiency in various cancer cells, with limited toxicity over normal hepato-cyte and prostate cells. Mouse PC3 xenograft studies showed 47 and 48 significantly reduced tumor growth.