1-((甲基磺酰基)甲基)-1H-吡唑-3-胺 | 1003011-35-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 亚胺内酰胺
• 中文名称: 1-((甲基磺酰基)甲基)-1H-吡唑-3-胺
• 英文名称: 1-((methylsulfonyl)methyl)-1H-pyrazol-3-amine
• 英文别名: 1-methanesulfonylmethyl-1H-pyrazol-3-ylamine；1-(methylsulfonylmethyl)pyrazol-3-amine
• CAS: 1003011-35-5
• 化学式: C₅H₉N₃O₂S
• 分子量: 175.211
• InChiKey: UUAIKKMNUHXYIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  86.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-((甲基磺酰基)甲基)-1H-吡唑-3-胺 、 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39%的产率得到N-(3-fluoro-4-((2-((1-((methylsulfonyl)methyl)-1H-pyrazol-3-yl)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-((甲基磺酰基)甲基)-3-硝基-1H-吡唑 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以97%的产率得到1-((甲基磺酰基)甲基)-1H-吡唑-3-胺
  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

• Pyrazole glucokinase activators
  申请人：Berthel Steven Joseph

  公开号：US20080021032A1

  公开（公告）日：2008-01-24

  Disclosed herein are pyrazole glucokinase activators of the formula (I) useful for the treatment of metabolic diseases and disorders, preferably diabetes mellitus.

  本文披露了一种式(I)的吡唑葡萄糖激酶激活剂，可用于治疗代谢性疾病和紊乱，尤其是糖尿病。
• Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity
  作者：Zhengsheng Zhan、Jing Ai、Qiufeng Liu、Yinchun Ji、Tiantian Chen、Yechun Xu、Meiyu Geng、Wenhu Duan

  DOI：10.1021/ml500066m

  日期：2014.6.12

  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.