N-((1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-3-(4-fluorophenyl)-1-phenyl-1H-pyrazole-4-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-((1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-3-(4-fluorophenyl)-1-phenyl-1H-pyrazole-4-carboxamide
• 英文别名: N-[[1-[(4-chlorophenyl)methyl]triazol-4-yl]methyl]-3-(4-fluorophenyl)-1-phenylpyrazole-4-carboxamide
• 化学式: C₂₆H₂₀ClFN₆O
• 分子量: 486.936
• InChiKey: BNKFLXCKPMUZJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  77.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(4-氟-苯基)-1-苯基-1H-吡唑-4-甲醛 在 sodium chlorite 、 copper(ll) sulfate pentahydrate 、 氨基磺酸 、 1-羟基苯并三唑 、 sodium ascorbate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 、 叔丁醇 为溶剂， 反应 29.33h， 生成 N-((1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-3-(4-fluorophenyl)-1-phenyl-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of N -((1-benzyl-1 H -1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1 H -pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors

  摘要：

  A series of new (N4(1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-Pyrazole-4-carboxamide derivatives (8-35) were designed, synthesized and evaluated as CDK1/Cdc2 inhibitors. Biological evaluation assays indicated that compounds 16 and 27 showed the most potent growth inhibitory activity against human cancer cell lines (MIAPaCa-2, MCF-7 and HeLa) with GI(50) values ranging from 0.13 to 0.7 mu M, compared with the positive control nocodazole (0.81-0.95 mu M). Flow cytometric analysis revealed that these compounds induce cell cycle arrest in the G2/M phase and Western blot analysis suggested that compound treatment resulted in reduction of CDK1 expression levels in MCF-7 cell line. Moreover, the apoptosis inducing effect of the compounds was studied using Hoechst staining, Rhoda mine 123 staining (MMP), carboxy-DCFDA staining (ROS), Annexin V-FITC assay. Based on these studies, two compounds 16 and 27 have been identified as promising new molecules that have the potential to be developed as leads. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.06.011

文献信息

• Design, synthesis and biological evaluation of N -((1-benzyl-1 H -1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1 H -pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors
  作者：V. Ganga Reddy、T. Srinivasa Reddy、V. Lakshma Nayak、Budaganaboyina Prasad、Adiyala Praveen Reddy、A. Ravikumar、Shaik Taj、Ahmed Kamal

  DOI：10.1016/j.ejmech.2016.06.011

  日期：2016.10

  A series of new (N4(1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-Pyrazole-4-carboxamide derivatives (8-35) were designed, synthesized and evaluated as CDK1/Cdc2 inhibitors. Biological evaluation assays indicated that compounds 16 and 27 showed the most potent growth inhibitory activity against human cancer cell lines (MIAPaCa-2, MCF-7 and HeLa) with GI(50) values ranging from 0.13 to 0.7 mu M, compared with the positive control nocodazole (0.81-0.95 mu M). Flow cytometric analysis revealed that these compounds induce cell cycle arrest in the G2/M phase and Western blot analysis suggested that compound treatment resulted in reduction of CDK1 expression levels in MCF-7 cell line. Moreover, the apoptosis inducing effect of the compounds was studied using Hoechst staining, Rhoda mine 123 staining (MMP), carboxy-DCFDA staining (ROS), Annexin V-FITC assay. Based on these studies, two compounds 16 and 27 have been identified as promising new molecules that have the potential to be developed as leads. (C) 2016 Elsevier Masson SAS. All rights reserved.