3-(4-chlorophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1H -pyrazole-1-carbothioamide | 686725-80-4

• 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-chlorophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1H -pyrazole-1-carbothioamide
• 英文别名: 5-(4-Chlorophenyl)-3-thiophen-2-yl-3,4-dihydropyrazole-2-carbothioamide
• CAS: 686725-80-4
• 化学式: C₁₄H₁₂ClN₃S₂
• 分子量: 321.854
• InChiKey: KVUODIKVVCDUSB-UHFFFAOYSA-N

物化性质

• 沸点：
  480.4±55.0 °C(Predicted)
• 密度：
  1.48±0.1 g/cm3(Predicted)

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：

  2-溴-4'-(三氟甲基)苯乙酮 、 3-(4-chlorophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1H -pyrazole-1-carbothioamide 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-chlorophenyl)-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：

  2-噻吩甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 3-(4-chlorophenyl)-5-(thiophen-2-yl)-4,5-dihydro-1H -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

• Novel 3, 3a, 4, 5, 6, 7-Hexahydroindazole and Arylthiazolylpyrazoline derivatives as Anti-inflammatory Agents
  作者：Magda N. A. Nasr、Shehta A. Said

  DOI：10.1002/ardp.200300796

  日期：2003.12

  the other intermediates 3, 5‐diaryl‐1‐thiocarbamoyl‐2‐pyrazolines 7a—d were reacted with the previously‐mentioned reagents and gave the corresponding 3, 5‐diaryl‐1‐(4‐aryl‐2‐thiazolyl)‐2‐pyrazolines 8a—h, 3, 5‐diaryl‐1‐(5‐arylidene‐4, 5‐dihydro‐4‐oxo‐2‐thiazolyl)‐2‐pyrazolines 9a—d and 3, 5‐diaryl‐1‐(thiazolo[4, 5‐b]quinoxalin‐2‐yl)‐2‐pyrazoline derivatives 10a, b, respectively. Some of the newly prepared

  合成了2-位取代的7-亚苄基-3, 3a, 4, 5, 6, 7-六氢- 3-苯基- 2H-吲唑的新系列。2, 6-双-亚苄基环己酮 (1) 与氨基硫脲在 NaOH 存在下的反应得到 3-H、3a-H 反式 2 和顺式 2a 非对映异构体的混合物，这些非对映异构体已通过分级重结晶分离。在乙酸和乙酸酐的混合物存在下，第一个中间体 2 与取代苯甲酰溴、芳香醛和氯乙酸相互作用，2, 3-二氯喹喔啉产生相应的 7-亚苄基-3, 3a, 4, 5, 6 , 7-六氢-3-苯基-2H-吲唑衍生物在2-位被4-芳基-2-噻唑基3a、b、5-亚芳基-4、5-二氢-4-氧代-2-噻唑基-4-噻唑基取代b 和噻唑并 [4, 5-b] quinoxalin-2-yl 5，分别。而且，其他中间体3, 5-二芳基- 1-硫代氨基甲酰基- 2-吡唑啉7a - d 与前面提到的试剂反应得到相应的3, 5-二芳基- 1-
• Heterocyclic compounds with different moieties: synthesis and evaluation of biological activities assisted with the computational study
  作者：Dursun Kısa、Esra Koç、Kübra Sena Baş Topcu、Rizvan İmamoğlu

  DOI：10.1080/07391102.2023.2268182

  日期：——

  In the present work, heterocyclic compounds containing different moieties, such as pyrazole and thiophene, were synthesized and screened for inhibitory potency against medicinal enzymes and bacteri...

  在本工作中，合成了含有不同基团的杂环化合物，如吡唑和噻吩，并筛选了对药用酶和细菌的抑制效力。
• 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
• Synthesis, biological evaluation and 3D-QSAR study of novel 4,5-dihydro-1H-pyrazole thiazole derivatives as BRAFV600E inhibitors
  作者：Meng-Yue Zhao、Yong Yin、Xiao-Wei Yu、Chetan B. Sangani、Shu-Fu Wang、Ai-Min Lu、Li-Fang Yang、Peng-Cheng Lv、Ming-Guo Jiang、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2014.11.029

  日期：2015.1

  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.