3-(4'-methoxyphenyl)-5-phenyl-1-thiocarbamoyl-2-pyrazoline | 153332-13-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(4'-methoxyphenyl)-5-phenyl-1-thiocarbamoyl-2-pyrazoline
• 英文别名: 3-(4-methoxyphenyl)-5-phenyl-2-pyrazoline-1-carbothioamide；pyrazoline-1-carbothioamide；3-(4-methoxyphenyl)-5-phenyl-4,5-dihydropyrazole-1-carbothioamide；5-(4-methoxyphenyl)-3-phenyl-3,4-dihydropyrazole-2-carboximidothioic acid
• CAS: 153332-13-9
• 化学式: C₁₇H₁₇N₃OS
• 分子量: 311.407
• InChiKey: FVLMPRHVNJXADJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 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-phenyl-1-thiocarbamoyl-2-pyrazoline 在 sodium acetate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 (Z)-2-(4-((2-(3-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-oxothiazol-5(4H)-ylidene)methyl)phenoxy)acetic acid
  参考文献：
  名称：

  用于抗炎剂噻唑/噻唑烷棒状吡唑啉衍生物设计的片段合并方法：合成、生物药理学评价和分子建模研究

  摘要：

  应用片段合并方法设计噻唑/噻唑烷酮棒状吡唑啉衍生物5a-e、6a-c、7和10a-d作为 COX-2 和 5-LOX 双重抑制剂。化合物5a、6a和6b是最有效的 COX-2 选择性抑制剂（IC 50 = 0.03–0.06 μM，SI = 282.7–472.9），对 5-LOX 具有高活性（IC 50  = 4.36–4.86 μM），而化合物5b和10a是活性和选择性5-LOX抑制剂，IC 50 分别为2.43和1.58 μM。大多数活性候选物6a的体内测定和组织病理学检查显示，与标准药物相比，炎症显着减少，安全性更高。化合物6a表现出与参考 COX-2 和 5-LOX 抑制剂（分别为塞来昔布和槲皮素）相同的方向和结合相互作用。因此，化合物6a已被确定为进一步优化和开发安全有效的抗炎药物的潜在先导化合物。

  DOI：

  10.1016/j.bioorg.2023.106724
• 作为产物：
  描述：

  对甲氧基苯乙酮 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 3-(4'-methoxyphenyl)-5-phenyl-1-thiocarbamoyl-2-pyrazoline
  参考文献：
  名称：

  通过抑制A549人肺癌细胞中的mTOR活性，发现新的荧光噻唑-吡唑啉衍生物作为自噬诱导剂。

  摘要：

  合成了一系列荧光噻唑-吡唑啉衍生物，并通过1 H NMR，13 C NMR和HRMS对其结构进行了表征。生物学评估表明，这些化合物可以在体外以剂量和时间依赖性方式有效抑制人非小细胞肺癌（NSCLC）A549细胞的生长，并在体内抑制肿瘤的生长。分析了化合物的构效关系（SAR）。进一步的机制研究表明，它们可以诱导自噬和细胞周期停滞，而对细胞坏死没有影响。化合物5e通过FKBP12抑制了mTOR的活性，这可以被mTOR激活剂和自噬抑制剂3BDO逆转。化合物5e在体内抑制生长，促进A549细胞自噬。此外，化合物5e具有良好的选择性，对正常的血管内皮细胞生长和正常的鸡胚绒膜尿囊膜（CAM）毛细管形成没有影响。因此，我们的研究为开发新型抗人肺癌抗癌药物提供了潜在的先导化合物。

  DOI：

  10.1038/s41419-020-02746-w

文献信息

• Synthesis of novel thiazolylpyrazoline derivatives and evaluation of their antimicrobial activities and cytotoxicities
  作者：Aouatef TABBI、Zafer Asım KAPLANCIKLI、Dahmane TEBBANI、Leyla YURTTAŞ、Zerrin CANTÜRK、Özlem ATLI、Merve BAYSAL、Gülhan TURAN-ZITOUNI

  DOI：10.3906/kim-1512-12

  日期：——

  Several novel thiazolylpyrazoline derivatives were synthesized by reacting substituted 3,5-diaryl-1-thiocarba\-moyl-2-pyrazolines with phenacylbromides. The structures of the synthesized compounds were confirmed by IR, $^1}$H NMR, $^13}$C NMR, and MS spectral data. Their antimicrobial activities against Staphylococcus aureus(ATCC-25923), Enterococcus faecalis} (ATCC-29212), Enterococcus faecalis (ATCC-51922), Listeria monocytogenes (ATCC-1911), Klebsiella pneumoniae (ATCC-700603), Pseudomonas aeruginosa (ATCC-27853), Escherichia coli (ATCC-35218), Escherichia coli (ATCC-25922), Candida albicans (ATCC-90028), Candida glabrata (ATCC-90030), Candida krusei (ATCC-6258), and Candida parapsilosis (ATCC-22019) were investigated. The compounds were also studied for their cytotoxic effects using a MTT assay. Compound 7c showed the highest antimicrobial activity, possessing the same potential as chloramphenicol against K. pneumonia, P. aeruginosa, and E. coli (ATCC-25923).

  通过苯乙酰溴与取代的3,5-二芳基-1-硫脲-2-吡唑啉反应，合成了几种新颖的噻唑啉基吡唑啉衍生物。通过IR、$^1}$H NMR、$^13}$C NMR和MS光谱数据确认了合成化合物的结构。研究了这些化合物对金黄色葡萄球菌(ATCC-25923)、粪肠球菌(ATCC-29212和ATCC-51922)、单核细胞增生李斯特菌(ATCC-1911)、肺炎克雷伯菌(ATCC-700603)、铜绿假单胞菌(ATCC-27853)、大肠埃希菌(ATCC-35218和ATCC-25922)、白色念珠菌(ATCC-90028)、光滑念珠菌(ATCC-90030)、克鲁斯念珠菌(ATCC-6258)和副克鲁斯念珠菌(ATCC-22019)的抗微生物活性。还通过MTT测定法研究了这些化合物的细胞毒性效应。化合物7c显示出最高的抗微生物活性，对肺炎克雷伯菌、铜绿假单胞菌和大肠埃希菌(ATCC-25923)具有与氯霉素相同的潜力。
• 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。
• Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors
  作者：Ke-Ming Qiu、Hai-Hong Wang、Li-Ming Wang、Yin Luo、Xian-Hui Yang、Xiao-Ming Wang、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2012.01.051

  日期：2012.3

  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.
• Chawla, Rakesh; Sahoo, Ujjwal; Arora, Anshu, Acta poloniae pharmaceutica, 2010, vol. 67, # 1, p. 55 - 61
  作者：Chawla, Rakesh、Sahoo, Ujjwal、Arora, Anshu、Sharma, Prabodh Chander、Radhakrishnan, Vijayaraj

  DOI：——

  日期：——