2-methyl-5-((methylsulfonyl)methyl)aniline | 1584220-22-3

• 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: 2-methyl-5-((methylsulfonyl)methyl)aniline
• 英文别名: 2-Methyl-5-(methylsulfonylmethyl)aniline
• CAS: 1584220-22-3
• 化学式: C₉H₁₃NO₂S
• 分子量: 199.274
• InChiKey: MBBJHFNWMWFKFR-UHFFFAOYSA-N

物化性质

• 熔点：
  93-94 °C
• 沸点：
  434.6±33.0 °C(predicted)
• 密度：
  1.231±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methyl-5-((methylsulfonyl)methyl)aniline 、 N-(4-((2-chloropyrimidin-4-yl)oxy)-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 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 为溶剂， 反应 2.0h， 以40%的产率得到N-(3-fluoro-4-((2-((2-methyl-5-((methylsulfonyl)methyl)phenyl)amino)pyrimidin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
  参考文献：
  名称：

  Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity

  摘要：

  Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed molecules for structure activity relationship (SAR) exploration. Some analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent antiproliferative effect against c-Met addictive cell lines with IC50 values ranged from 0.33 to 1.7 mu M. In addition, a cocrystal structure of c-Met in complex with 3h has been determined, which reveals the binding mode of c-Met to its inhibitor and helps to interpret the SAR of the analogues.

  DOI：

  10.1021/ml500066m
• 作为产物：
  描述：

  1-methyl-4-((methylsulfonyl)methyl)-2-nitrobenzene 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以95%的产率得到2-methyl-5-((methylsulfonyl)methyl)aniline
  参考文献：
  名称：

  Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity

  摘要：

  Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed molecules for structure activity relationship (SAR) exploration. Some analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent antiproliferative effect against c-Met addictive cell lines with IC50 values ranged from 0.33 to 1.7 mu M. In addition, a cocrystal structure of c-Met in complex with 3h has been determined, which reveals the binding mode of c-Met to its inhibitor and helps to interpret the SAR of the analogues.

  DOI：

  10.1021/ml500066m

文献信息

• Design, synthesis and biological evaluation of O-linked indoles as VEGFR-2 kinase inhibitors (I)
  作者：Guo-Rui Gao、Meng-Yuan Li、Lin-Jiang Tong、Li-Xin Wei、Jian Ding、Hua Xie、Wen-Hu Duan

  DOI：10.1016/j.cclet.2015.07.016

  日期：2015.9

  Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a series of O-linked indoles as potent inhibitors of VEGFR-2. Among these compounds, 18 showed significant anti-angiogenesis activities via VEGFR-2 in enzymatic proliferation assays, with IC50 value of 3.8 nmol/L. Kinase selectivity profiling revealed that 18 was a multitargeted inhibitor, and it also exhibited good potency against VEGFR-1, PDGFR-alpha and beta. (C) 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.