2-hydroxy-4-oxo-4-(2-phenanthryl)but-2-enoic acid ethyl ester | 1314023-78-3

• 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: 2-hydroxy-4-oxo-4-(2-phenanthryl)but-2-enoic acid ethyl ester
• 英文别名: ethyl 2-hydroxy-4-oxo-4-phenanthr-2-yl-but-2-enoate
• CAS: 1314023-78-3
• 化学式: C₂₀H₁₆O₄
• 分子量: 320.345
• InChiKey: XEZIMVCFLRVPOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  63.6
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-hydroxy-4-oxo-4-(2-phenanthryl)but-2-enoic acid ethyl ester 在 palladium on activated charcoal 、 氢气 、 对甲苯磺酸 作用下， 以 甲醇 、 乙醇 、 乙酸乙酯 为溶剂， 120.0 ℃ 、482.64 kPa 条件下， 生成 1-(4-aminophenyl)-N-methyl-5-(phenanthren-2-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
• 作为产物：
  描述：

  2-乙酰基菲 、 草酸二乙酯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以82%的产率得到2-hydroxy-4-oxo-4-(2-phenanthryl)but-2-enoic acid ethyl ester
  参考文献：
  名称：

  新型选择性碳酸酐酶IX抑制剂：二芳基吡唑-苯磺酰胺的合成和药理评价

  摘要：

  碳酸酐酶（CA）IX的表达在缺氧时增加，并且由于与不良预后，肿瘤进展和pH调节相关，因此被提议作为治疗靶标。我们报告了新型的人类碳酸酐酶（hCA）抑制剂4-（5-芳基-2-羟甲基-吡唑-1-基）-苯磺酰胺类的合成和药理学评估。为了模拟这种新的酶抑制剂家族在hCA IX活性位点内的结合模式，进行了分子建模研究。药理研究表明，在参数纳摩尔范围内，hCA IX的抑制力很高。这项研究表明磺酰胺基在间位上的位置1-苯基吡唑的相对于我们的化合物的hCA II的选择性增加了hCA IX。使用阿霉素作为细胞毒剂并在选定的CA IX抑制剂存在下，对乳腺癌MDA-MB-231细胞进行了体外抗增殖筛选。结果表明，用1μMCA IX抑制剂将阿霉素在低氧环境中的细胞毒性效率（以IC 50值表示）恢复到20％的水平。

  DOI：

  10.1016/j.bmc.2012.10.029

文献信息

• New FAAH inhibitors based on 3-carboxamido-5-aryl-isoxazole scaffold that protect against experimental colitis
  作者：Virginie Andrzejak、Giulio G. Muccioli、Mathilde Body-Malapel、Jamal El Bakali、Madjid Djouina、Nicolas Renault、Philippe Chavatte、Pierre Desreumaux、Didier M. Lambert、Régis Millet

  DOI：10.1016/j.bmc.2011.04.057

  日期：2011.6

  Growing evidence suggests a role for the endocannabinoid (EC) system, in intestinal inflammation and compounds inhibiting anandamide degradation offer a promising therapeutic option for the treatment of inflammatory bowel diseases. In this paper, we report the first series of carboxamides derivatives possessing FAAH inhibitory activities. Among them, compound 39 displayed significant inhibitory FAAH activity (IC50 = 0.088 mu M) and reduced colitis induced by intrarectal administration of TNBS. (C) 2011 Elsevier Ltd. All rights reserved.