5-(2-(3-aminophenoxy)-5-(methylsulfonyl)phenyl)-7-methylimidazo[1,5-a]pyrazin-8(7H)-one

• 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: 5-(2-(3-aminophenoxy)-5-(methylsulfonyl)phenyl)-7-methylimidazo[1,5-a]pyrazin-8(7H)-one
• 英文别名: 5-[2-(3-Aminophenoxy)-5-methylsulfonylphenyl]-7-methylimidazo[1,5-a]pyrazin-8-one；5-[2-(3-aminophenoxy)-5-methylsulfonylphenyl]-7-methylimidazo[1,5-a]pyrazin-8-one
• 化学式: C₂₀H₁₈N₄O₄S
• 分子量: 410.453
• InChiKey: RQZUMQWSVKPPQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  间甲苯磺酰氯 、 5-(2-(3-aminophenoxy)-5-(methylsulfonyl)phenyl)-7-methylimidazo[1,5-a]pyrazin-8(7H)-one 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以94.5%的产率得到3-methyl-N-(3-(2-(7-methyl-8-oxo-7,8-dihydroimidazo[1,5-a]pyrazin-5-yl)-4-(methylsulfonyl)phenoxy)phenyl)benzenesulfonamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 7-methylimidazo[1,5- a ]pyrazin-8(7 H )-one derivatives as BRD4 inhibitors

  摘要：

  BRD4 is an attractive target for antitumor due to its important role in regulation of gene transcription. In this paper, we synthesized a series of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as potent BRD4 inhibitors and evaluated their BRD4 inhibitory activities in vitro and anti-proliferation effects on tumor cells. Gratifyingly, compound 10j exhibited robust potency of BRD4(1) and BRD4(2) inhibition with IC50 values of 130 and 76 nM respectively. Docking studies were performed to explain the structure-activity relationship. Furthermore, compound 10j potently inhibited cell proliferation in BRD4-sensitive cell lines HL-60 and MV4-11 with IC50 value of 0.57 and 0.18 mu M respectively. Activity on BRD4-independent K562 cell was weaker than on BRD4-sensitive lines. Overall, these results suggest that compound 10j is a potential BRD4 inhibitor deserving further investigation for cancer treatment. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.03.008
• 作为产物：
  描述：

  对氟苯甲砜 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 硫酸 、 potassium acetate 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 64.0h， 生成 5-(2-(3-aminophenoxy)-5-(methylsulfonyl)phenyl)-7-methylimidazo[1,5-a]pyrazin-8(7H)-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 7-methylimidazo[1,5- a ]pyrazin-8(7 H )-one derivatives as BRD4 inhibitors

  摘要：

  BRD4 is an attractive target for antitumor due to its important role in regulation of gene transcription. In this paper, we synthesized a series of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as potent BRD4 inhibitors and evaluated their BRD4 inhibitory activities in vitro and anti-proliferation effects on tumor cells. Gratifyingly, compound 10j exhibited robust potency of BRD4(1) and BRD4(2) inhibition with IC50 values of 130 and 76 nM respectively. Docking studies were performed to explain the structure-activity relationship. Furthermore, compound 10j potently inhibited cell proliferation in BRD4-sensitive cell lines HL-60 and MV4-11 with IC50 value of 0.57 and 0.18 mu M respectively. Activity on BRD4-independent K562 cell was weaker than on BRD4-sensitive lines. Overall, these results suggest that compound 10j is a potential BRD4 inhibitor deserving further investigation for cancer treatment. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.03.008

文献信息

• Design, synthesis and biological evaluation of 7-methylimidazo[1,5- a ]pyrazin-8(7 H )-one derivatives as BRD4 inhibitors
  作者：Leilei Zhao、Yifei Yang、Yahui Guo、Lingyun Yang、Jian Zhang、Jinpei Zhou、Huibin Zhang

  DOI：10.1016/j.bmc.2017.03.008

  日期：2017.4

  BRD4 is an attractive target for antitumor due to its important role in regulation of gene transcription. In this paper, we synthesized a series of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as potent BRD4 inhibitors and evaluated their BRD4 inhibitory activities in vitro and anti-proliferation effects on tumor cells. Gratifyingly, compound 10j exhibited robust potency of BRD4(1) and BRD4(2) inhibition with IC50 values of 130 and 76 nM respectively. Docking studies were performed to explain the structure-activity relationship. Furthermore, compound 10j potently inhibited cell proliferation in BRD4-sensitive cell lines HL-60 and MV4-11 with IC50 value of 0.57 and 0.18 mu M respectively. Activity on BRD4-independent K562 cell was weaker than on BRD4-sensitive lines. Overall, these results suggest that compound 10j is a potential BRD4 inhibitor deserving further investigation for cancer treatment. (C) 2017 Elsevier Ltd. All rights reserved.