4-[3-(4-chloro-3-methoxyphenyl)-1-(3-aminophenyl)-1H-pyrazol-4-yl]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[3-(4-chloro-3-methoxyphenyl)-1-(3-aminophenyl)-1H-pyrazol-4-yl]pyridine
• 英文别名: 3-(3-(4-chloro-3-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-1-yl)benzenamine；3-[3-(4-Chloro-3-methoxyphenyl)-4-pyridin-4-ylpyrazol-1-yl]aniline；3-[3-(4-chloro-3-methoxyphenyl)-4-pyridin-4-ylpyrazol-1-yl]aniline
• 化学式: C₂₁H₁₇ClN₄O
• 分子量: 376.845
• InChiKey: AYAXLMNOQFKBRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[3-(4-chloro-3-methoxyphenyl)-1-(3-aminophenyl)-1H-pyrazol-4-yl]pyridine 在 三溴化硼 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.5h， 生成 N-(3-(3-(4-chloro-3-hydroxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-1-yl)phenyl)benzamide
  参考文献：
  名称：

  New triarylpyrazoles as broad-spectrum anticancer agents: Design, synthesis, and biological evaluation

  摘要：

  A new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold was designed and synthesized. Their in vitro antiproliferative activities against NCI-60 cell line panel were tested. Most of the compounds showed strong and broad-spectrum antiproliferative activities. Compound 18 exerted sub-micromolar IC50 values over all the subpanels of nine different cancer types. Its IC50 value over MDA-MB-435 melanoma cell line was 27 nM. Compounds 10-13, 22, and 23 possessing urea spacer exerted lethal effect over the NCI-60 panel with mean %inhibitions more than 100% in single-dose testing. Compounds 13 and 23 with urea linker and 3',5'-bis(trifluoromethyl)phenyl terminal ring showed the highest mean %inhibition over the NCI-60 panel in single-dose testing, and showed high potencies and broad-spectrum anticancer activities in five-dose testing. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.067
• 作为产物：
  描述：

  4-氯-3-甲氧基苯甲酸甲酯 在 copper(l) iodide 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 一水合肼 、 L-脯氨酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 28.0h， 生成 4-[3-(4-chloro-3-methoxyphenyl)-1-(3-aminophenyl)-1H-pyrazol-4-yl]pyridine
  参考文献：
  名称：

  具有不同杂环末端部分的新三芳基吡唑衍生物的设计，合成，体外有效的抗增殖活性和激酶抑制作用。

  摘要：

  已经设计并合成了具有不同杂环末端基团的一系列新的三芳基吡唑衍生物。化合物1h-j和1l在10μM的浓度下对58种癌细胞系表现出最高的平均抑制百分比，因此接下来在5剂量测试模式下进行检测以检测其IC50值。与索拉非尼作为参考化合物进行比较后，这四种化合物显示出更强的抗增殖活性。其中，在10μM浓度下，具有58个细胞系的化合物通过乙烯连接基具有N-乙基哌嗪基和N-苄基哌嗪基末端部分的化合物1j和1l显示出最大的平均抑制百分比值（分别为97.72和107.18％）。化合物1j在几种癌细胞系中的IC50值处于亚微摩尔级（0.26〜0.38μM）。而且，

  DOI：

  10.1080/14756366.2019.1653292

文献信息

• Design, synthesis, <i>in vitro</i> potent antiproliferative activity, and kinase inhibitory effects of new triarylpyrazole derivatives possessing different heterocycle terminal moieties
  作者：Mahmoud M. Gamal El-Din、Mohammed I. El-Gamal、Mohammed S. Abdel-Maksoud、Kyung Ho Yoo、Chang-Hyun Oh

  DOI：10.1080/14756366.2019.1653292

  日期：2019.1.1

  triarylpyrazole derivatives having different heterocycle terminal groups have been designed and synthesised. Compounds 1h-j and 1l exhibited the highest mean percentage inhibition against the 58 cancer cell lines at a concentration of 10 μM, and thus were next examined in 5-dose testing mode to detect their IC50 value. The four compounds showed stronger antiproliferative activities upon comparing their

  已经设计并合成了具有不同杂环末端基团的一系列新的三芳基吡唑衍生物。化合物1h-j和1l在10μM的浓度下对58种癌细胞系表现出最高的平均抑制百分比，因此接下来在5剂量测试模式下进行检测以检测其IC50值。与索拉非尼作为参考化合物进行比较后，这四种化合物显示出更强的抗增殖活性。其中，在10μM浓度下，具有58个细胞系的化合物通过乙烯连接基具有N-乙基哌嗪基和N-苄基哌嗪基末端部分的化合物1j和1l显示出最大的平均抑制百分比值（分别为97.72和107.18％）。化合物1j在几种癌细胞系中的IC50值处于亚微摩尔级（0.26〜0.38μM）。而且，
• New triarylpyrazoles as broad-spectrum anticancer agents: Design, synthesis, and biological evaluation
  作者：Mohammed I. El-Gamal、Yi Seul Park、Dae Yoon Chi、Kyung Ho Yoo、Chang-Hyun Oh

  DOI：10.1016/j.ejmech.2013.04.067

  日期：2013.7

  A new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold was designed and synthesized. Their in vitro antiproliferative activities against NCI-60 cell line panel were tested. Most of the compounds showed strong and broad-spectrum antiproliferative activities. Compound 18 exerted sub-micromolar IC50 values over all the subpanels of nine different cancer types. Its IC50 value over MDA-MB-435 melanoma cell line was 27 nM. Compounds 10-13, 22, and 23 possessing urea spacer exerted lethal effect over the NCI-60 panel with mean %inhibitions more than 100% in single-dose testing. Compounds 13 and 23 with urea linker and 3',5'-bis(trifluoromethyl)phenyl terminal ring showed the highest mean %inhibition over the NCI-60 panel in single-dose testing, and showed high potencies and broad-spectrum anticancer activities in five-dose testing. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Evaluation of the Inhibitory Effects of Pyridylpyrazole Derivatives on LPS-Induced PGE2 Productions and Nitric Oxide in Murine RAW 264.7 Macrophages
  作者：Mahmoud M. Gamal El-Din、Mohammed I. El-Gamal、Young-Do Kwon、Su-Yeon Kim、Hee-Soo Han、Sang-Eun Park、Chang-Hyun Oh、Kyung-Tae Lee、Hee-Kwon Kim

  DOI：10.3390/molecules26216489

  日期：——

  A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds 1a–m have first been assessed for cytotoxicity against RAW 264.7 macrophages to determine their non-cytotoxic concentration(s) for anti-inflammatory testing to make sure that the inhibition of PGE2 and NO production would not be caused by cytotoxicity. It was found that compounds 1f and 1m were the most potent PGE2 inhibitors with IC50 values of 7.1 and 1.1 μM, respectively. In addition, these compounds also showed inhibitory effects of 11.6% and 37.19% on LPS-induced NO production, respectively. The western blots analysis of COX-2 and iNOS showed that the PGE2 and NO inhibitory effect of compound 1m are attributed to inhibition of COX-2 and iNOS protein expression through inactivation of p38.

  一系列十三个三芳基吡唑类似物被研究作为抑制RAW 264.7巨噬细胞中脂多糖（LPS）诱导的前列腺素E2（PGE2）和一氧化氮（NO）产生的抑制剂。首先评估了目标化合物1a-m对RAW 264.7巨噬细胞的细胞毒性，以确定它们的非细胞毒浓度，用于抗炎测试，以确保PGE2和NO产生的抑制不是由细胞毒性引起的。发现化合物1f和1m是最有效的PGE2抑制剂，IC50值分别为7.1和1.1μM。此外，这些化合物还分别显示对LPS诱导的NO产生的抑制效果为11.6%和37.19%。COX-2和iNOS的免疫印迹分析显示，化合物1m的PGE2和NO抑制效应归因于通过抑制p38使COX-2和iNOS蛋白表达失活。