N1-((3-chlorophenyl)(pyridin-2-yl)methyl)-4-(methylsulfonyl)-N2-(pyrimidin-2-yl)benzene-1,2-diamine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N1-((3-chlorophenyl)(pyridin-2-yl)methyl)-4-(methylsulfonyl)-N2-(pyrimidin-2-yl)benzene-1,2-diamine
• 化学式: C₂₃H₂₀ClN₅O₂S
• 分子量: 465.963
• InChiKey: JZZKDASEJHKEGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.87
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  96.87
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N1-((3-chlorophenyl)(pyridin-2-yl)methyl)-4-(methylsulfonyl)-N2-(pyrimidin-2-yl)benzene-1,2-diamine 在 column Chiralcel OD 作用下， 以 乙醇 、 正庚烷 为溶剂， 以96.6%的产率得到
  参考文献：
  名称：

  New Potent DOT1L Inhibitors for in Vivo Evaluation in Mouse

  摘要：

  In MLL-rearranged cancer cells, disruptor of telomeric silencing 1-like protein (DOT1L) is aberrantly recruited to ectopic loci leading to local hypermethylation of H3K79 and consequently misexpression of leukemogenic genes. A structure-guided optimization of a HTS hit led to the discovery of DOT1L inhibitors with subnanomolar potency, allowing testing of the therapeutic principle of DOT1L inhibition in a preclinical mouse tumor xenograft model. Compounds displaying good exposure in mouse and nanomolar inhibition of target gene expression in cells were obtained and tested in vivo.

  DOI：

  10.1021/acsmedchemlett.9b00452
• 作为产物：
  描述：

  2-硝基-4-甲砜基氯苯 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 铁粉 、 caesium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 21.0h， 生成 N1-((3-chlorophenyl)(pyridin-2-yl)methyl)-4-(methylsulfonyl)-N2-(pyrimidin-2-yl)benzene-1,2-diamine
  参考文献：
  名称：

  New Potent DOT1L Inhibitors for in Vivo Evaluation in Mouse

  摘要：

  In MLL-rearranged cancer cells, disruptor of telomeric silencing 1-like protein (DOT1L) is aberrantly recruited to ectopic loci leading to local hypermethylation of H3K79 and consequently misexpression of leukemogenic genes. A structure-guided optimization of a HTS hit led to the discovery of DOT1L inhibitors with subnanomolar potency, allowing testing of the therapeutic principle of DOT1L inhibition in a preclinical mouse tumor xenograft model. Compounds displaying good exposure in mouse and nanomolar inhibition of target gene expression in cells were obtained and tested in vivo.

  DOI：

  10.1021/acsmedchemlett.9b00452

文献信息

• New Potent DOT1L Inhibitors for <i>in Vivo</i> Evaluation in Mouse
  作者：Frédéric Stauffer、Andreas Weiss、Clemens Scheufler、Henrik Möbitz、Christian Ragot、Kim S. Beyer、Keith Calkins、Daniel Guthy、Michael Kiffe、Bernard Van Eerdenbrugh、Ralph Tiedt、Christoph Gaul

  DOI：10.1021/acsmedchemlett.9b00452

  日期：2019.12.12

  In MLL-rearranged cancer cells, disruptor of telomeric silencing 1-like protein (DOT1L) is aberrantly recruited to ectopic loci leading to local hypermethylation of H3K79 and consequently misexpression of leukemogenic genes. A structure-guided optimization of a HTS hit led to the discovery of DOT1L inhibitors with subnanomolar potency, allowing testing of the therapeutic principle of DOT1L inhibition in a preclinical mouse tumor xenograft model. Compounds displaying good exposure in mouse and nanomolar inhibition of target gene expression in cells were obtained and tested in vivo.