5-(4-chlorophenyl)-3-(4-methylphenyl)-4,5-dihydro-1H-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: 5-(4-chlorophenyl)-3-(4-methylphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide
• 英文别名: 3-(4-chlorophenyl)-5-(4-methylphenyl)-3,4-dihydropyrazole-2-carbothioamide
• 化学式: C₁₇H₁₆ClN₃S
• 分子量: 329.853
• InChiKey: GJPMHQYGBHVAIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  73.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)-3-(4-methylphenyl)-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-(5-(4-chlorophenyl)-3-(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：

  对甲基苯乙酮 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 5-(4-chlorophenyl)-3-(4-methylphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide
  参考文献：
  名称：

  Novel pyrazoline linked acyl thiourea pharmacophores as antimicrobial, urease, amylase and α-glucosidase inhibitors: design, synthesis, SAR and molecular docking studies

  摘要：

  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。

  DOI：

  10.1039/d3ra06812a

文献信息

• Synthesis, Molecular Modeling Studies, and Selective Inhibitory Activity against Monoamine Oxidase of 1-Thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1<i>H</i>)- pyrazole Derivatives
  作者：Franco Chimenti、Elias Maccioni、Daniela Secci、Adriana Bolasco、Paola Chimenti、Arianna Granese、Olivia Befani、Paola Turini、Stefano Alcaro、Francesco Ortuso、Roberto Cirilli、Francesco La Torre、Maria C. Cardia、Simona Distinto

  DOI：10.1021/jm040903t

  日期：2005.11.1

  The separated enantiomers were then submitted to in vitro biological evaluation. The selectivity of the (-)-(S)-1 enantiomer against MAO-B increases twice and a half, while the selectivity of the (-)-(S)-4 enantiomer against MAO-A triples. Both the MAO-A and MAO-B isoforms respectively of the 1O5W and 1GOS models deposited in the Protein Data Bank were considered in the computational study. The docking

  合成了一系列新型的1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-（1H）-吡唑衍生物，并研究了选择性抑制单胺氧化酶A和B同工型（MAO）活性的能力。 ）。所有合成的化合物均显示出对MAO-A和MAO-B同种型均具有高活性，Ki值分别在27和4 nM之间以及在50和1.5 nM之间，除了一些对MAO-B具有抑制活性的衍生物。微摩尔范围。知道立体化学可能是生物活性的重要调节剂，我们进行了最有效，选择性和手性化合物的半制备色谱对映体分离。然后将分离的对映异构体进行体外生物学评估。（-）-（S）-1对映体对MAO-B的选择性提高了两倍半，而（-）-（S）-4对映体对MAO-A的选择性则提高了三倍。在计算研究中考虑了分别存放在蛋白质数据库中的1O5W和1GOS模型的MAO-A和MAO-B亚型。对接研究是使用几种计算方法进行的，目的是提出MAO对映选择性化合物1和4的可能结合方式。
• [EN] PYRIDAZIN-3(2H)-ONE DERIVATIVES WHICH ARE SELECTIVE INHIBITORS OF THE ISOFORM B OF MONOAMINE OXIDASE<br/>[ES] DERIVADOS DE PIRIDAZIN-3(2H)-ONA INHIBIDORES SELECTIVOS DE LA ISOFORMA B DE LA MONOAMINOOXIDASA<br/>[FR] DÉRIVÉS DE PYRIDAZINE-3(2H)-ONE, INHIBITEURS SÉLECTIFS DE L'ISOFORME B DE LA MONOAMINE OXYDASE
  申请人：UNIV VIGO

  公开号：WO2015132427A1

  公开（公告）日：2015-09-11

  Esta invención se refiere a derivados de piridazin-3(2H)-ona de estructura general (I), (II) y (III), que son inhibidores selectivos de la MAO-B, y a su uso para preparar medicamentos destinados a tratar trastornos derivados de la hiperactividad de la MAO-B, en particular trastornos degenerativos del sistema nervioso central (SNC), como la enfermedad de Pakinson (EP), la enfermedad de Alzheimer (EA) y otras demencias. Se trata de derivados de piridazin-3(2H)-ona que presentan fragmentos de ditiocarbamato enlazados a la posición 4, 5 o 6 a través de una cadena alquílica de longitud variable (n=l, 2, 3). Esta invención también se dirige a la preparación de dichos compuestos.
• 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.
• 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。