N-(4-methyl-3-(4-(pyridin-3-yl)-1H-pyrazol-1-yl)phenyl)-4-(pyrrolidin-1-ylmethyl)benzamide

• 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: N-(4-methyl-3-(4-(pyridin-3-yl)-1H-pyrazol-1-yl)phenyl)-4-(pyrrolidin-1-ylmethyl)benzamide
• 英文别名: N-[4-methyl-3-(4-pyridin-3-ylpyrazol-1-yl)phenyl]-4-(pyrrolidin-1-ylmethyl)benzamide
• 化学式: C₂₇H₂₇N₅O
• 分子量: 437.544
• InChiKey: ASJUWXZPJDVCQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  63
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-4-硝基甲苯 在 盐酸 、 四(三苯基膦)钯 、 palladium on activated charcoal 、 氢气 、 三乙胺 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 7.67h， 生成 N-(4-methyl-3-(4-(pyridin-3-yl)-1H-pyrazol-1-yl)phenyl)-4-(pyrrolidin-1-ylmethyl)benzamide
  参考文献：
  名称：

  Design, synthesis, and biological activity of phenyl-pyrazole derivatives as BCR–ABL kinase inhibitors

  摘要：

  4-(Pyridin-3-yl)-1H-pyrazol-1-yl-phenyl-3-benzamide derivatives have been proposed as new BCR-ABL tyrosine kinase inhibitors by using combinational strategies of scaffold hopping and conformational constraint. In the present study, a series of 4-(pyridin-3-yl)-1H-pyrazol-1-yl-phenyl-3-benzamide derivatives were synthesized and their activities against BCR-ABL1 kinase in vitro were evaluated by using Kinase-Glo assay. All new compounds showed from moderate to potent activities against wild-type (wt) BCR-ABL1 kinase with an IC50 range from 14.2 to 326.0 nM. Among them, seven compounds exhibited BCR-ABL1 kinase inhibitory activities with IC50 values less than 50 nM. Compound 7a displayed the most potent inhibitory activity to BCR-ABL kinase (IC50: 14.2 nM). Docking simulation was performed for compounds 7a and 7i into the BCR-ABL kinase structure active site to determine the probable binding model. The preliminary structure-activity relationship was discussed. The interesting activities of these compounds may make them promising candidates as therapeutic agents for chronic myelogenous leukemia. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.083

文献信息

• Design, synthesis, and biological activity of phenyl-pyrazole derivatives as BCR–ABL kinase inhibitors
  作者：Liming Hu、Yuyan Zheng、Zhipeng Li、Yujie Wang、Yongjuan Lv、Xuemei Qin、Chengchu Zeng

  DOI：10.1016/j.bmc.2015.04.083

  日期：2015.7

  4-(Pyridin-3-yl)-1H-pyrazol-1-yl-phenyl-3-benzamide derivatives have been proposed as new BCR-ABL tyrosine kinase inhibitors by using combinational strategies of scaffold hopping and conformational constraint. In the present study, a series of 4-(pyridin-3-yl)-1H-pyrazol-1-yl-phenyl-3-benzamide derivatives were synthesized and their activities against BCR-ABL1 kinase in vitro were evaluated by using Kinase-Glo assay. All new compounds showed from moderate to potent activities against wild-type (wt) BCR-ABL1 kinase with an IC50 range from 14.2 to 326.0 nM. Among them, seven compounds exhibited BCR-ABL1 kinase inhibitory activities with IC50 values less than 50 nM. Compound 7a displayed the most potent inhibitory activity to BCR-ABL kinase (IC50: 14.2 nM). Docking simulation was performed for compounds 7a and 7i into the BCR-ABL kinase structure active site to determine the probable binding model. The preliminary structure-activity relationship was discussed. The interesting activities of these compounds may make them promising candidates as therapeutic agents for chronic myelogenous leukemia. (C) 2015 Elsevier Ltd. All rights reserved.