3-(4-methyl-6-phenyl-pyrimidin-2-ylsulfanyl)propionic acid

• 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: 3-(4-methyl-6-phenyl-pyrimidin-2-ylsulfanyl)propionic acid
• 英文别名: 3-(4-Methyl-6-phenylpyrimidin-2-yl)sulfanylpropanoic acid；3-(4-methyl-6-phenylpyrimidin-2-yl)sulfanylpropanoic acid
• 化学式: C₁₄H₁₄N₂O₂S
• 分子量: 274.343
• InChiKey: NICUZINNNJUSNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  88.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(4-methyl-6-phenyl-pyrimidin-2-ylsulfanyl)propionic acid 在 1-丙基磷酸酐 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-(2,4-difluorophenyl)-3-((4-methyl-6-phenylpyrimidin-2-yl)sulfonyl)propanamide
  参考文献：
  名称：

  2-磺酰基嘧啶通过半胱氨酸烷基化靶向驱动蛋白HSET

  摘要：

  通过共价靶向半胱氨酸残基，2-磺酰基嘧啶可抑制驱动蛋白HSET的酶活性，并诱导多极有丝分裂和氧化应激，从而强调了这些烷基化剂在细胞中的多效作用。

  DOI：

  10.1002/ejoc.201900586
• 作为产物：
  描述：

  2,4-二氯-6-甲基嘧啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.25h， 生成 3-(4-methyl-6-phenyl-pyrimidin-2-ylsulfanyl)propionic acid
  参考文献：
  名称：

  Discovery of 2-(Cyclohexylmethylamino)pyrimidines as a New Class of Reversible Valosine Containing Protein Inhibitors

  摘要：

  Valosine-containing protein (VCP), also known as p97 or cdc48 in yeast, is a highly abundant protein belonging to the AAA ATPase family involved in a number of essential cellular functions, including ubiquitin-proteasome mediated protein degradation, Golgi reassembly, transcription activation, and cell cycle control. Altered expression of VCP has been detected in many cancer types sometimes associated with poor prognosis. Furthermore, VCP mutations are causative of some neurodegenerative disorders. In this paper we report the discovery, synthesis, and structure-activity relationships of substituted 2-aminopyrimidines, representing a new class of reversible VCP inhibitors. This class of compounds, identified in a HTS campaign against recombinant VCP, has been progressively expanded and manipulated to increase biochemical potency and gain cellular activity.

  DOI：

  10.1021/jm501313x

文献信息

• 2‐Sulfonylpyrimidines Target the Kinesin HSET via Cysteine Alkylation
  作者：Tim Förster、Erchang Shang、Kenshiro Shimizu、Emiko Sanada、Beate Schölermann、Mylene Huebecker、Gernot Hahne、Maria Pascual López‐Alberca、Petra Janning、Nobumoto Watanabe、Sonja Sievers、Fabrizio Giordanetto、Takeshi Shimizu、Slava Ziegler、Hiroyuki Osada、Herbert Waldmann

  DOI：10.1002/ejoc.201900586

  日期：2019.9

  2‐Sulfonylpyrimidines were identified to inhibit the enzymatic activity of the kinesin HSET by covalently targeting cysteine residues and to induce multipolar mitoses and oxidative stress, thus emphasizing the pleiotropic effects of these alkylating agents in cells.

  通过共价靶向半胱氨酸残基，2-磺酰基嘧啶可抑制驱动蛋白HSET的酶活性，并诱导多极有丝分裂和氧化应激，从而强调了这些烷基化剂在细胞中的多效作用。
• Discovery of 2-(Cyclohexylmethylamino)pyrimidines as a New Class of Reversible Valosine Containing Protein Inhibitors
  作者：Giovanni Cervi、Paola Magnaghi、Daniela Asa、Nilla Avanzi、Alessandra Badari、Daniela Borghi、Michele Caruso、Alessandra Cirla、Liviana Cozzi、Eduard Felder、Arturo Galvani、Fabio Gasparri、Antonio Lomolino、Steven Magnuson、Beatrice Malgesini、Ilaria Motto、Maurizio Pasi、Simona Rizzi、Barbara Salom、Graziella Sorrentino、Sonia Troiani、Barbara Valsasina、Thomas O’Brien、Antonella Isacchi、Daniele Donati、Roberto D’Alessio

  DOI：10.1021/jm501313x

  日期：2014.12.26

  Valosine-containing protein (VCP), also known as p97 or cdc48 in yeast, is a highly abundant protein belonging to the AAA ATPase family involved in a number of essential cellular functions, including ubiquitin-proteasome mediated protein degradation, Golgi reassembly, transcription activation, and cell cycle control. Altered expression of VCP has been detected in many cancer types sometimes associated with poor prognosis. Furthermore, VCP mutations are causative of some neurodegenerative disorders. In this paper we report the discovery, synthesis, and structure-activity relationships of substituted 2-aminopyrimidines, representing a new class of reversible VCP inhibitors. This class of compounds, identified in a HTS campaign against recombinant VCP, has been progressively expanded and manipulated to increase biochemical potency and gain cellular activity.