5-thiophen-2-yl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole | 259170-37-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-thiophen-2-yl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole
• CAS: 259170-37-1
• 化学式: C₁₄H₉F₃N₂S
• 分子量: 294.3
• InChiKey: CHPDRFQTLXLRTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  56.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2R,3S)-2-(thiophene-2-carbonyl)-3-[4-(trifluoromethyl)phenyl]cyclopropane-1,1-dicarbonitrile 在 一水合肼 作用下， 以 乙二醇二甲醚 为溶剂， 以78%的产率得到5-thiophen-2-yl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole
  参考文献：
  名称：

  含对三氟甲基苯基的反式-1,2-环丙烷的简便制备方法及其在吡唑和环丙烷环稠合哒嗪酮衍生物的构建中的应用

  摘要：

  描述了一种用于制备含有对-三氟甲基苯基3的高度官能化的反式-1,2-环丙烷的简便方法。鉮溴化物1与缺电子烯烃反应2中K的存在2 CO 3，以提供3在中度至良好的产率立体选择性。该方法已成功地应用于环丙烷环稠合的哒嗪酮衍生物4或吡唑衍生物5的构建。

  DOI：

  10.1016/j.tet.2008.05.016

文献信息

• Discovery of 5-aryl-3-thiophen-2-yl-1H-pyrazoles as a new class of Hsp90 inhibitors in hepatocellular carcinoma
  作者：Samy Mohamady、Muhammad I. Ismail、Samar M. Mogheith、Yasmeen M. Attia、Scott D. Taylor

  DOI：10.1016/j.bioorg.2019.103433

  日期：2020.1

  Although hepatocellular carcinoma (HCC)-related mortality has increased over the past decades, treatment options are still very limited, underlining the need for developing new therapeutic strategies. The molecular chaperone heat shock protein 90 (Hsp90) plays a key role in post-translational maturation of many oncogenic client proteins that are important for survival and proliferation of cancer cells. Thus, inhibitors of Hsp90 are promising targets for many cancer types. In this study, 15 diarylpyrazole compounds were screened against MCF7 and HepG2 cell lines. Compound 8, which contained a thiophene group, demonstrated the highest antiproliferative activity against HepG2 cells having an IC50, of 0.083 mu M. Four additional diarylpyrazoles, each containing a thiophene group, were prepared and screened for antiproliferative activity. None of these four compounds exhibited superior activity to compound 8 on HepG2 cells. Therefore, compound 8 was selected for further in vitro assays. Cell cycle arrest was observed at the G2 phase in compound 8-treated cells. Compound 8 also caused a 7.7-fold increase in caspase-3. These results confirm the apoptotic effect of compound 8 on HepG2 cells. Moreover, compound 8 inhibited Hsp90 (IC50, = 2.67 +/- 0.18 mu M) in an in vitro assay and caused a 70.8% reduction in Hsp90 levels in a HepG2 cell-based assay. Additionally, compound 8 caused significant reduction in the levels of Hsp90 client proteins (Akt, c-Met, c-Raf, and EGFR) and a 1.57-fold increase in Hsp70. Molecular docking studies were also performed to predict the binding mode of compound 8 and followed by molecular dynamics simulations to give further insights into the binding mode of 8.