1-(4-(2-aminoacetamido)phenyl)-N-ethyl-5-(phenanthren-3-yl)-1H-pyrazole-3-carboxamide | 1333146-34-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 1-(4-(2-aminoacetamido)phenyl)-N-ethyl-5-(phenanthren-3-yl)-1H-pyrazole-3-carboxamide
• 英文别名: 1-[4-[(2-aminoacetyl)amino]phenyl]-N-ethyl-5-phenanthren-3-ylpyrazole-3-carboxamide
• CAS: 1333146-34-1
• 化学式: C₂₈H₂₅N₅O₂
• 分子量: 463.539
• InChiKey: ZNSZTBSRNWSFKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-乙酰基菲 在 盐酸 、 palladium on activated charcoal 、 氢气 、 sodium hydride 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙酸乙酯 为溶剂， 20.0~120.0 ℃ 、482.64 kPa 条件下， 生成 1-(4-(2-aminoacetamido)phenyl)-N-ethyl-5-(phenanthren-3-yl)-1H-pyrazole-3-carboxamide
  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

• ANTICANCER P21-ACTIVATED KINASE INHIBITORS
  申请人：Ohio State Innovation Foundation

  公开号：US20140323538A1

  公开（公告）日：2014-10-30

  Compounds according to formula I: wherein Ar is a fused aryl group, R 1 is selected from alkyl and aryl amides, CF 3 , and CH 2 OH, and R 2 is selected from hydrogen, —C(═O)CH 2 NH 2 , and —C(═O)CH 2 CH 2 NH 2 are described. The compounds are effective for inhibiting p21-activated kinases, and can be used for prevention and treatment of cancer.

  根据公式I描述的化合物中，Ar是融合芳基基团，R1可选择烷基和芳基酰胺、三氟甲基和羟甲基，R2可选择氢、—C(═O)CH2NH2和—C(═O)CH2CH2NH2。这些化合物对抑制p21激活激酶具有有效性，可用于癌症的预防和治疗。
• US9156790B2
  申请人：——

  公开号：US9156790B2

  公开（公告）日：2015-10-13
• Identification and Characterization of a Novel Integrin-Linked Kinase Inhibitor
  作者：Su-Lin Lee、En-Chi Hsu、Chih-Chien Chou、Hsiao-Ching Chuang、Li-Yuan Bai、Samuel K. Kulp、Ching-Shih Chen

  DOI：10.1021/jm2007744

  日期：2011.9.22

  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.