2-(3-(4-fluorophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-methoxyphenyl)thiazole | 929507-06-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(3-(4-fluorophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-methoxyphenyl)thiazole
• 英文别名: 2-[5-(4-Fluorophenyl)-3-thiophen-2-yl-3,4-dihydropyrazol-2-yl]-4-(4-methoxyphenyl)-1,3-thiazole
• CAS: 929507-06-2
• 化学式: C₂₃H₁₈FN₃OS₂
• 分子量: 435.546
• InChiKey: HNFFFHDRLZCPFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  94.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氟苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.17h， 生成 2-(3-(4-fluorophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-methoxyphenyl)thiazole
  参考文献：
  名称：

  Synthesis, biological evaluation and 3D-QSAR study of novel 4,5-dihydro-1H-pyrazole thiazole derivatives as BRAFV600E inhibitors

  摘要：

  Many reports implied that the BRAF serine/threonine kinase was mutated in various types of human tumors, which were related with cell growth, survival and differentiation. To provide new therapeutic opportunities, a series of novel 4,5-dihydro-1H-pyrazole derivatives (6a-10d) containing thiazole moiety as potential V600E mutant BRAF kinase (BRAF(V600E)) inhibitors were designed and synthesized. All compounds were evaluated in vitro for anticancer activities against WM266.4 human melanoma cell line and breast cancer MCF-7 cell line. Compound 10d displayed the most potential antiproliferative activity with an IC50 value of 0.12μM against cell line WM266.4 and 0.16μM against MCF-7 with positive control Sorafenib. Results of the inhibitory activity against BRAF(V600E) revealed that compound 10d was bearing the best bioactivity with IC50 of 0.05μM as well. On the basis of the result of flow cytometry, with the dose of compound 10d increasing, more and more cancer cell gradually encountered apoptosis or died, which indicated the compound 10d could induce remarkable apoptosis of MCF-7 and WM266.4 cells in a dose dependent manner. Furthermore, docking simulation of inhibitor analogues and 3D-QSAR modeling provided potential binding model and further knowledge of pharmacophore.

  DOI：

  10.1016/j.bmc.2014.11.029

文献信息

• Discovery and modification of sulfur-containing heterocyclic pyrazoline derivatives as potential novel class of β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors
  作者：Yu-Shun Yang、Fei Zhang、Chao Gao、Yan-Bin Zhang、Xiao-Liang Wang、Jian-Feng Tang、Jian Sun、Hai-Bin Gong、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2012.05.091

  日期：2012.7

  A series of sulfur-containing heterocyclic pyrazoline derivatives (C1-C18; D1-D9) have been synthesized and purified (all are new except one) to be screened for FabH inhibitory activity. Compound C14 showed the most potent biological activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis (MIC values: 1.56-3.13 mu g/mL), being comparable with the positive control, while D6 performed the best in the thiazolidinone series (MIC values: 3.13-6.25 mu g/mL). They also demonstrated strong broad-spectrum antimicrobial activity. Compounds C14 and D6 exhibited the most potent E. coli FabH inhibitory activity with IC50 of 4.6 and 8.4 mu M, respectively, comparable with the positive control DDCP (IC50 = 2.8 mu M). Docking simulation was performed to position compound C14 and D6 into the E. coli FabH structure active site to determine the probable binding model. The structurally modification of previous compounds and the attempt in innovative target have brought a positive progress. (C) 2012 Published by Elsevier Ltd.