3-(4-bromophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1 H - pyrazole-1-carbothioamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-bromophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1 H - pyrazole-1-carbothioamide
• 英文别名: 5-(4-Bromophenyl)-3-thiophen-2-yl-3,4-dihydropyrazole-2-carbothioamide
• 化学式: C₁₄H₁₂BrN₃S₂
• 分子量: 366.305
• InChiKey: WMLOBFMWOLIRGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-bromophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1 H - pyrazole-1-carbothioamide 、 2-溴-4'-(三氟甲基)苯乙酮 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以49%的产率得到2-(3-(4-bromophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-(trifluoromethyl)phenyl)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
• 作为产物：
  描述：

  4-溴苯乙酮 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 3-(4-bromophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1 H - pyrazole-1-carbothioamide
  参考文献：
  名称：

  作为潜在琥珀酸脱氢酶抑制剂的新型 4,5-二氢-1H-吡唑衍生物：设计、合成、晶体结构、生物活性和分子建模

  摘要：

  设计、合成了28 种新的 4, 5-二氢-1 H-吡唑衍生物，并通过 IR、1 H NMR、13 C NMR 和 HRMS 对其进行了表征。化合物2j的晶体结构通过单晶X射线衍射表征。对它们对五种植物病原真菌的抗真菌活性进行了评估：二倍体球孢菌、指状青霉、轮孢菌、谷丝核菌和核盘菌。结果显示，它们中的大多数在 20 µg/mL 时表现出显着的抗真菌活性。化合物3a (EC 50  = 0.138 µg/mL) 和3f (EC 50 = 0.081 µg/mL) 对核盘菌表现出优异的抗真菌活性，并且比商业杀菌剂戊硫菌灵 (EC 50  = 0.250 µg/mL)具有更好的功效。同时，测定了生物活性化合物对琥珀酸脱氢酶（SDH）的抑制活性。结果表明，化合物3a (IC 50  = 0.200 µg/mL) 和3f (IC 50  = 0.104 µg/mL) 具有比吡噻菌胺(IC 50  = 0

  DOI：

  10.1016/j.molstruc.2021.131537

文献信息

• 5-杂环取代的吡唑类化合物及其在农药中的 应用
  申请人：西华大学

  公开号：CN111039933B

  公开（公告）日：2021-03-02

  本发明涉及5‑杂环取代的吡唑类化合物及其在农药中的应用，属于农药技术领域。本发明解决的技术问题是提供一种可作为农用杀菌剂和种子发芽促进剂的新化合物。该化合物的结构式为式I所示，其中，X为氧、硫或氮，Y为氧、硫或氮，R为甲基、甲氧基、羟甲基、氯或溴。该化合物对植物病原真菌有较好的抑制活性，且对蔬菜种子的发芽有较好的促进作用，将为新农药的创制奠定较好的基础。
• 一类含吡唑啉与噻吩(或呋喃)结构的噻唑啉酮 类衍生物及其制法与应用
  申请人：南京大学

  公开号：CN103304560B

  公开（公告）日：2016-05-18

  一类含吡唑啉与噻吩结构的噻唑啉酮类衍生物，其特征是它有如下通式：结构式中R为：一类含吡唑啉与呋喃结构的噻唑啉酮类衍生物，其特征是它有如下通式：结构式中R为：本发明的噻唑啉酮类衍生物可做潜在的抗菌和抗肿瘤药物。本发明公开了其制法。
• 一类含吡唑啉与噻吩(或呋喃)结构的噻唑类衍 生物及其制法与用途
  申请人：南京大学

  公开号：CN103304559B

  公开（公告）日：2016-05-18

  一类同时含吡唑啉与噻吩结构或同时含有吡唑啉与呋喃结构的噻唑类衍生物，它具有如下通式：结构式中R1为：R2为：H，-OCH3；X为：S，O；一类含吡唑啉与呋喃结构的噻唑类衍生物，它具有如下通式：结构式中R1为：R2为-OCH3；X为O。本发明的噻唑类衍生物可做潜在的抗菌和抗肿瘤药物。本发明公开了其制法。
• 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.
• Novel 4,5-dihydro-1H-pyrazole derivatives as potential succinate dehydrogenase inhibitors: design, synthesis, crystal structure, biological activity and molecular modeling
  作者：Tingting Zhang、Hui Liu、Tong Lu、Guilan Zhang、Tingting Xiao、Wei Cheng、Jingwen Wang、Wenjing Jiang、Xiaorong Tang

  DOI：10.1016/j.molstruc.2021.131537

  日期：2022.2

  Twenty-eight new 4, 5-dihydro-1H-pyrazole derivatives were designed, synthesized and characterized by IR, 1H NMR, 13C NMR and HRMS. The crystal structure of compound 2j was characterized by single crystal X-ray diffraction. Their antifungal activities were evaluated against five plant pathogenic fungi: Coniella diplodiella, Penicillium digitatum, Physalospora piricola, Rhizoctonia cerealis and Sclerotinia

  设计、合成了28 种新的 4, 5-二氢-1 H-吡唑衍生物，并通过 IR、1 H NMR、13 C NMR 和 HRMS 对其进行了表征。化合物2j的晶体结构通过单晶X射线衍射表征。对它们对五种植物病原真菌的抗真菌活性进行了评估：二倍体球孢菌、指状青霉、轮孢菌、谷丝核菌和核盘菌。结果显示，它们中的大多数在 20 µg/mL 时表现出显着的抗真菌活性。化合物3a (EC 50  = 0.138 µg/mL) 和3f (EC 50 = 0.081 µg/mL) 对核盘菌表现出优异的抗真菌活性，并且比商业杀菌剂戊硫菌灵 (EC 50  = 0.250 µg/mL)具有更好的功效。同时，测定了生物活性化合物对琥珀酸脱氢酶（SDH）的抑制活性。结果表明，化合物3a (IC 50  = 0.200 µg/mL) 和3f (IC 50  = 0.104 µg/mL) 具有比吡噻菌胺(IC 50  = 0