N-methyl-3-(1-(4-nitrophenyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide | 1333147-01-5

• 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-methyl-3-(1-(4-nitrophenyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide
• 英文别名: N-methyl-3-[1-(4-nitrophenyl)-5-[4-[4-(trifluoromethyl)phenyl]phenyl]pyrazol-3-yl]propanamide
• CAS: 1333147-01-5
• 化学式: C₂₆H₂₁F₃N₄O₃
• 分子量: 494.473
• InChiKey: KUJLAPHFSKFJNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-methyl-3-(1-(4-nitrophenyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 、 乙酸乙酯 为溶剂， 170.0 ℃ 、482.64 kPa 条件下， 反应 32.0h， 生成 OSU-T315
  参考文献：
  名称：

  Identification and Characterization of a Novel Integrin-Linked Kinase Inhibitor

  摘要：

  Integrin-linked kinase (ILK) represents a relevant target for cancer therapy in light of its role in promoting oncogenesis and tumor progression. Through the screening of an in-house focused compound library, we identified N-methyl-3-(1-(4-(piperazin-1-yl)phenyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide (22) as a novel ILK inhibitor (IC50, 0.6 mu M), which exhibited high in vitro potency against a panel of prostate and breast cancer cell lines (IC50, 1-2.5 mu M), while normal epithelial cells were unaffected. Compound 22 facilitated the dephosphorylation of Akt at Ser-473 and other ILK targets, including glycogen synthase kinase-3 beta and myosin light chain. Moreover, 22 suppressed the expression of the transcription/translation factor YB-1 and its targets HER2 and EGFR in PC-3 cells, which could be rescued by the stable expression of constitutively active ILK. Evidence indicates that 22 induced autophagy and apoptosis, both of which were integral to its antiproliferative activity. Together, this broad spectrum of mechanisms underlies the therapeutic potential of 22 in cancer treatment, which is manifested by its in vivo efficacy as a single oral agent in suppressing PC-3 xenograft tumor growth.

  DOI：

  10.1021/jm2007744
• 作为产物：
  描述：

  (Z)-ethyl 4-hydroxy-6-oxo-6-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)hex-4-enoate 在 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 反应 16.17h， 生成 N-methyl-3-(1-(4-nitrophenyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide
  参考文献：
  名称：

  Identification and Characterization of a Novel Integrin-Linked Kinase Inhibitor

  摘要：

  Integrin-linked kinase (ILK) represents a relevant target for cancer therapy in light of its role in promoting oncogenesis and tumor progression. Through the screening of an in-house focused compound library, we identified N-methyl-3-(1-(4-(piperazin-1-yl)phenyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide (22) as a novel ILK inhibitor (IC50, 0.6 mu M), which exhibited high in vitro potency against a panel of prostate and breast cancer cell lines (IC50, 1-2.5 mu M), while normal epithelial cells were unaffected. Compound 22 facilitated the dephosphorylation of Akt at Ser-473 and other ILK targets, including glycogen synthase kinase-3 beta and myosin light chain. Moreover, 22 suppressed the expression of the transcription/translation factor YB-1 and its targets HER2 and EGFR in PC-3 cells, which could be rescued by the stable expression of constitutively active ILK. Evidence indicates that 22 induced autophagy and apoptosis, both of which were integral to its antiproliferative activity. Together, this broad spectrum of mechanisms underlies the therapeutic potential of 22 in cancer treatment, which is manifested by its in vivo efficacy as a single oral agent in suppressing PC-3 xenograft tumor growth.

  DOI：

  10.1021/jm2007744

文献信息

• ANTIBACTERIAL PROTEIN KINASE INHIBITORS
  申请人：The Ohio State University

  公开号：US20150258100A1

  公开（公告）日：2015-09-17

  Methods of treating bacterial infection by in a subject by administering a pharmaceutical composition including a celecoxib derivative are described. The compounds are particularly useful for treating infection by bacteria capable of growing inside macrophages, such as Myocobacteria tuberculosis.
• US9457031B2
  申请人：——

  公开号：US9457031B2

  公开（公告）日：2016-10-04