3-(4-methoxyphenyl)-5-(p-tolyl)-2-pyrazoline-1-carbothioamide | 153332-15-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(4-methoxyphenyl)-5-(p-tolyl)-2-pyrazoline-1-carbothioamide
• 英文别名: 5-(4-Methoxyphenyl)-3-(4-methylphenyl)-3,4-dihydropyrazole-2-carbothioamide
• CAS: 153332-15-1
• 化学式: C₁₈H₁₉N₃OS
• 分子量: 325.434
• InChiKey: FTXPCRLZLNNVFY-UHFFFAOYSA-N

物化性质

• 熔点：
  168-170 °C
• 沸点：
  494.5±55.0 °C(predicted)
• 密度：
  1.23±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-methoxyphenyl)-5-(p-tolyl)-2-pyrazoline-1-carbothioamide 、 溴乙酸 在 sodium acetate 、 乙酸酐 、 溶剂黄146 作用下， 以80%的产率得到2-(3-(4-methoxyphenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors

  摘要：

  A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and synthesized and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory activity (IC50 = 0.24 mu M for EGFR and IC50 = 1.07 mu M for HER-2). Antiproliferative assay results indicated that compound E28 owned high antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with IC50 value of 0.30, 0.54, and 0.70 mu M, respectively. Docking simulation was further performed to position compound E28 into the EGFR active site to determine the probable binding model. Based on the preliminary results, compound E28 with potent inhibitory activity in tumor growth would be a potential anticancer agent. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.051
• 作为产物：
  描述：

  对甲基苯甲醛 在 potassium hydroxide 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 3-(4-methoxyphenyl)-5-(p-tolyl)-2-pyrazoline-1-carbothioamide
  参考文献：
  名称：

  噻唑基-吡唑啉衍生物的合成、抗癌评价及分子对接研究

  摘要：

  具有不同活性的噻唑和吡唑啉杂环结构的分子杂交似乎是开发新抗癌化合物的有趣策略。本研究介绍了 11 种新的噻唑基-吡唑啉衍生物 ( 7a - k ) 的合成，并通过 MTT 法评估了它们对人肺癌 (A549) 和人黑色素瘤 (A375) 细胞系的体外抗增殖活性。与阳性参考药物厄洛替尼（ A549 中的IC 50 = 34.16 µM，A375 中的 IC 50  = 25.85 µM）相比，四种化合物（7e、7h、7j和7k ）) 被确定为对两种细胞系最活跃（尤其是化合物7k，IC 50  = A549 中的 20.28 µM 和 A375 中的 16.08 µM）。此外，通过抑制基质金属蛋白酶 2、9 (MMP-2、9) 和环加氧酶 2 (COX-2) 的表达，选择了这些有效化合物来研究它们的抗转移和抗炎特性。在 A549 细胞中，暴露于化合物7e和7j后，COX-2 表达降低，而化合物7e、7j和7k减少

  DOI：

  10.1016/j.bmcl.2022.129105

文献信息

• Design, synthesis, and SAR study of novel 4,5-dihydropyrazole-Thiazole derivatives with anti-inflammatory activities for the treatment of sepsis
  作者：Zhen Zhang、Peichang Cao、Mengyuan Fang、Tingfeng Zou、Jihong Han、Yajun Duan、Huajian Xu、Xiaoxiao Yang、Qing-Shan Li

  DOI：10.1016/j.ejmech.2021.113743

  日期：2021.12

  and thiazole derivatives have many biological functions, especially in the aspect of anti-inflammation. According to the strategy of pharmacophore combination, we introduced thiazole moiety into dihydropyrazole skeleton to design and synthesize a novel series of 2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-methylthiazole derivatives, and evaluated their anti-inflammatory activities for sepsis treatment

  全身炎症反应综合征是脓毒症的一个主要特征，脓毒症是全世界主要的死亡原因之一。据报道，3,5-二芳基-4,5-二氢吡唑和噻唑衍生物具有许多生物学功能，特别是在抗炎方面。根据药效团结合的策略，我们将噻唑部分引入二氢吡唑骨架，设计合成了一系列新型2-(3,5-diphenyl-4,5-dihydro-1 H -pyrazol-1-yl)-4-甲基噻唑衍生物，并评估了它们在脓毒症治疗中的抗炎活性。通过它们对 LPS 诱导的 RAW264.7 细胞中一氧化氮 (NO) 释放的抑制活性和最佳化合物E26进行初步构效关系 (SAR) 分析表现出比阳性对照治疗消炎痛和地塞米松更有效的抗炎活性。在进一步的机制研究中，我们的结果表明，化合物E26显着抑制白细胞介素-1β (IL-1β)、肿瘤坏死因子-α (TNF-α)、NO 的产生，并抑制诱导型一氧化氮合酶 (iNOS) 的表达， cyclooxygenase-2
• Synthesis, characterization, molecular docking and in vitro anticancer activity of 3-(4-methoxyphenyl)-5-substituted phenyl-2-pyrazoline-1- carbothioamide
  作者：Benupani Sahu、Rajapandi R、Avik Maji、Abhik Paul、Tanushree Singha、Tapan Kumar Maity

  DOI：10.26452/ijrps.v12i2.4759

  日期：——

  In the present study, eight numbers of new 3- (4-methoxy phenyl)-5-substituted phenyl-2-pyrazoline-1-carbothioamide (5a-h) have been synthesized from 1- (4-methoxy phenyl)-3- (substituted phenyl)-prop-2-en-1-one (3a-h) and structurally characterized by using FT-IR, 1H NMR, 13C NMR, Mass and Elemental analysis. The synthesized molecules were biologically evaluated for their in vitro anticancer activity against human breast adenocarcinoma (MCF-7), liver cancer (Hep-G2) and leukaemia cancer (K-562) cell line using Sulforhodamine B (SRB) bioassay technique. From the all synthesized compounds 5a, 5c, 5d, and 5e exhibited potent anticancer activity (GI50= <10µg/ml) as compared to the controlled drug 5-Fluorouracil (5-FU) (GI50=44.5µg/ml) and Adriamycin (ADR) (GI50= <10µg/ml) on MCF-7 cell lines. Besides this, all the synthesized compounds have exhibited moderate activity against human liver cancer (Hep-G2) and leukaemia cancer (K-562) cell lines. In addition, molecular docking studies were also explored in order to study the probable binding specificity into the active site of Epidermal Growth Factor Receptor tyrosine kinase (EGFR) (PDB ID: 1M17) using Molegro Virtual Docker Evaluation 2013 6.0.1 (MVD). Based on the molecular docking result, it was found that compound 5a exhibited the best interaction with the above target (i.e., EGFR) by interacting with specific amino acid residues such as: Thr 766, Gin 767, Thr 830, Cys 575, Ala 719 and Met 769.

  在这项研究中，从1- (4-甲氧基苯基)-3- (取代苯基)-丙-2-烯-1-酮 (3a-h) 合成了八种新的3- (4-甲氧基苯基)-5-取代苯基-2-吡唑啉-1-羰基硫脲 (5a-h)。利用FT-IR、1H NMR、13C NMR、质谱和元素分析对这些合成分子进行了结构表征。通过Sulforhodamine B (SRB) 生物测定技术，对这些合成分子在体外抗癌活性进行了生物学评价，针对人类乳腺腺癌 (MCF-7)、肝癌 (Hep-G2) 和白血病 (K-562) 细胞系。在所有合成化合物中，5a、5c、5d 和5e 表现出强大的抗癌活性 (GI50= <10µg/ml)，相比之下，对照药物5-氟尿嘧啶 (5-FU) (GI50=44.5µg/ml) 和阿霉素 (ADR) (GI50= <10µg/ml) 在MCF-7细胞系中的活性较弱。此外，所有合成化合物对人类肝癌 (Hep-G2) 和白血病 (K-562) 细胞系表现出中等活性。另外，还进行了分子对接研究，以研究这些化合物可能与表皮生长因子受体酪氨酸激酶 (EGFR) 的活性位点的结合特异性。根据分子对接结果，发现化合物5a 与上述靶点 (即EGFR) 有最好的相互作用，与特定氨基酸残基如：Thr 766、Gin 767、Thr 830、Cys 575、Ala 719 和Met 769 发生相互作用。
• Potent Alkaline Phosphatase Inhibitors, Pyrazolo-Oxothiazolidines: Synthesis, Biological Evaluation, Molecular Docking, and Kinetic Studies
  作者：Narges Hosseini Nasab、Hussain Raza、Rok Su Shim、Mubashir Hassan、Andrzej Kloczkowski、Song Ja Kim

  DOI：10.3390/ijms232113262

  日期：——

  To develop new alkaline phosphatase inhibitors (ALP), a series of pyrazolo-oxothiazolidine derivatives were synthesized and biologically assessed, and the results showed that all of the synthesized compounds significantly inhibited ALP. Specifically, compound 7g displayed the strongest inhibitory activity (IC50 = 0.045 ± 0.004 μM), which is 116-fold more active than monopotassium phosphate (IC50 =

  为了开发新的碱性磷酸酶抑制剂 (ALP)，合成了一系列吡唑并氧代噻唑烷衍生物并进行了生物学评估，结果表明所有合成的化合物均能显着抑制 ALP。具体而言，化合物7g显示出最强的抑制活性 (IC 50 = 0.045 ± 0.004 μM)，比作为标准参考的磷酸二氢钾 (IC 50 = 5.242 ± 0.472 μM)活性高 116 倍。该系列中最有效的化合物（7g) 检查其与酶结合的模式，并显示为与目标酶非竞争性结合。检测了这些化合物的抗氧化活性以研究自由基清除作用。此外，采用MTT法评估了它们对MG-63人骨肉瘤细胞活力的毒性作用，所有化合物在4 μM时对细胞均无毒性作用。还进行了计算研究以检查配体与碱性磷酸酶的结合亲和力，结果表明所有化合物在靶标的活性位点内均显示出良好的结合能值。因此，这些新型吡唑并氧代噻唑烷衍生物可能被用作有效和选择性碱性磷酸酶抑制剂的有前途的药效团。
• Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents
  作者：Peng-Cheng Lv、Dong-Dong Li、Qing-Shan Li、Xiang Lu、Zhu-Ping Xiao、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2011.07.010

  日期：2011.9

  Fourty-two thiazolyl-pyrazoline derivatives were synthesized to screen for their EGFR kinase inhibitory activity. Compound 4-(4-chlorophenyl)-2-(3-(3,4-dimethylphenyl)-5-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl) thiazole (11) displayed the most potent EGFR TK inhibitory activity with IC(50) of 0.06 mu M, which was comparable to the positive control. Molecular docking results indicated that compound 11 was nicely bound to the EGFR kinase. Compound 11 also showed significant antiproliferative activity against MCF-7 with IC(50) of 0.07 mu M, which would be a potential anticancer agent. (C) 2011 Elsevier Ltd. All rights reserved.
• New direction in the reaction of thiocarboxamides with N-substituted maleimides
  作者：R. V. Rudenko、S. A. Komykhov、S. M. Desenko

  DOI：10.1007/s10593-009-0377-5

  日期：2009.8