3-(4-chlorophenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide | 1214740-85-8

• 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-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide
• 英文别名: 5-(4-chlorophenyl)-3-(4-fluorophenyl)-3,4-dihydropyrazole-2-carbothioamide
• CAS: 1214740-85-8
• 化学式: C₁₆H₁₃ClFN₃S
• 分子量: 333.817
• InChiKey: YMWVSFOVYFSNAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  73.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-chlorophenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide 、 溴乙酸 在 sodium acetate 、 乙酸酐 、 溶剂黄146 作用下， 以81%的产率得到2-(3-(4-chlorophenyl)-5-(4-fluorophenyl)-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：

  对氯苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.17h， 生成 3-(4-chlorophenyl)-5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide
  参考文献：
  名称：

  新型 1-(4-取代-噻唑-2-基)-3,5-二(杂)芳基-吡唑啉衍生物的合成和对人COX-1的选择性抑制活性

  摘要：

  3,5-二(杂)芳基-1-硫代氨基甲酰基-2-反应得到新型1-(4-乙基羧酸酯-噻唑-2-基)-3,5-二(杂)芳基-2-吡唑啉衍生物吡唑啉与α-溴-丙酮酸乙酯。合成的化合物通过光谱数据得到证实，并进行了分析，以评估它们在体外抑制人类环氧合酶 (hCOX) 两种异构体的能力。一些衍生物（化合物 5、6、13、16 和 17）在微摩尔范围内对 hCOX-1 显示出有希望的选择性，并且显示出与参考药物（吲哚美辛、双氯芬酸）相似或更好的选择性指数。在（4-取代-噻唑-2-基）吡唑啉衍生物的 C3 上与 4-取代苯基或杂芳基相连的 C5 上引入苯基或 4-F-苯环提高了对 hCOX-的活性1.

  DOI：

  10.1002/ardp.201200249

文献信息

• Synthesis and Characterization of Novel 2-(1,2,3-Triazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazoles and 2-(4,5-Dihydro-1H-pyrazol-1-yl)-4-(1H-1,2,3-triazol-4-yl)thiazoles
  作者：Benson M. Kariuki、Bakr F. Abdel-Wahab、Hanan A. Mohamed、Mohamed S. Bekheit、Gamal A. El-Hiti

  DOI：10.3390/molecules27248904

  日期：——

  Reactions of 1-(5-methyl)-1H-1,2,3-triazol-4-yl)ethan-1-ones and benzaldehydes in ethanol under basic conditions gave the corresponding chalcones. Reactions of the chalcones combined with thiosemicarbazide in dry ethanol containing sodium hydroxide afforded the corresponding pyrazolin-N-thioamides. Reactions of the synthesized pyrazolin-N-thioamides and several ketones (namely, ethyl 2-chloro-3-oxobutanoate

  在碱性条件下，1-(5-甲基)-1H-1,2,3-三唑-4-基)乙-1-酮和苯甲醛在乙醇中发生反应，得到相应的查耳酮。在含有氢氧化钠的干燥乙醇中，查耳酮与硫代氨基甲酰肼反应生成相应的吡唑啉-N-硫代酰胺。将合成的吡唑啉-N-硫酰胺与几种酮（即 2-氯-3-氧代丁酸乙酯、2-溴乙酰基苯并呋喃和肼酰氯）反应，可得到相应的新型 2-(1,2,3-三唑-4-基)-4,5-二氢-1H-吡唑-1-基)噻唑，产率高（77-90%）。此外，在碱性条件下，通过与 N-吡唑啉硫酰胺和 4-溴乙酰基-1,2,3-三唑反应，高产率（84-87%）地获得了 2-(4,5-二氢-1H-吡唑-1-基)-4-(1H-1,2,3-三唑-4-基)噻唑。六种新合成杂环的结构通过 X 射线晶体学得到了证实。
• Novel pyrazoline linked acyl thiourea pharmacophores as antimicrobial, urease, amylase and α-glucosidase inhibitors: design, synthesis, SAR and molecular docking studies
  作者：Aamer Saeed、Atteeque Ahmed、Main Bilal Haider、Hammad Ismail、Khizar Hayat、Ghulam Shabir、Hesham R. El-Seedi

  DOI：10.1039/d3ra06812a

  日期：——

  IC₅₀ values of the new synthesized pyrazoline-acyl thioureas revealed 5b and 5g as potent urease inhibitors. Whilst compound 5b is a potent α-glucosidase inhibitor, compound 5f is a potent amylase inhibitor, compound 5b is a potent antioxidant.

  新合成的吡唑啉酰基硫脲类化合物的 IC50 值显示，5b 和 5g 是强效的脲酶抑制剂。化合物 5b 是一种强效的 α-葡萄糖苷酶抑制剂，化合物 5f 是一种强效的淀粉酶抑制剂，化合物 5b 则是一种强效的抗氧化剂。
• Synthesis and inhibitory activity against human monoamine oxidase of N1-thiocarbamoyl-3,5-di(hetero)aryl-4,5-dihydro-(1 H )-pyrazole derivatives
  作者：Franco Chimenti、Simone Carradori、Daniela Secci、Adriana Bolasco、Bruna Bizzarri、Paola Chimenti、Arianna Granese、Matilde Yáñez、Francisco Orallo

  DOI：10.1016/j.ejmech.2009.11.003

  日期：2010.2

  A series of N1-thiocarbamoyl-3,5-di(hetero)aryl-4,5-dihydro-(1H)-pyrazole derivatives has been synthesized and assayed for their ability to inhibit the activity of the A and B isoforms of human monoamine oxidase (hMAO). Some of these compounds were endowed with a selective inhibitory activity against hMAO-B in the micromolar range. The most active of the series is the compound 13, N1-thiocarbamoyl-3-(fur-2'-yl)-5-(4'-fluoro-phenyl)-4,5-dihydro-(1H)-pyrazole, with IC50 2.75 +/- 0.81 mu M value and selectivity ratio of 25, which is the best candidate for further investigations. (C) 2009 Elsevier Masson SAS. All rights reserved.
• 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.
• Synthesis and Selective Inhibitory Activity Against Human COX-1 of Novel 1-(4-Substituted-thiazol-2-yl)-3,5-di(hetero)aryl-pyrazoline Derivatives
  作者：Simone Carradori、Daniela Secci、Adriana Bolasco、Celeste De Monte、Matilde Yáñez

  DOI：10.1002/ardp.201200249

  日期：2012.12

  (compounds 5, 6, 13, 16, and 17) displayed promising selectivity against hCOX‐1 in the micromolar range and were shown to have a selectivity index similar or better than the reference drugs (indometacin, diclofenac). The introduction of a phenyl or a 4‐F‐phenyl ring on the C5 associated with a 4‐substituted phenyl or a heteroaryl group on the C3 of (4‐substituted‐thiazol‐2‐yl)pyrazoline derivatives improved

  3,5-二(杂)芳基-1-硫代氨基甲酰基-2-反应得到新型1-(4-乙基羧酸酯-噻唑-2-基)-3,5-二(杂)芳基-2-吡唑啉衍生物吡唑啉与α-溴-丙酮酸乙酯。合成的化合物通过光谱数据得到证实，并进行了分析，以评估它们在体外抑制人类环氧合酶 (hCOX) 两种异构体的能力。一些衍生物（化合物 5、6、13、16 和 17）在微摩尔范围内对 hCOX-1 显示出有希望的选择性，并且显示出与参考药物（吲哚美辛、双氯芬酸）相似或更好的选择性指数。在（4-取代-噻唑-2-基）吡唑啉衍生物的 C3 上与 4-取代苯基或杂芳基相连的 C5 上引入苯基或 4-F-苯环提高了对 hCOX-的活性1.