3-(4-Fluorophenyl)-1-[4-(methanesulfonyl)phenyl]prop-2-en-1-one | 819792-59-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 3-(4-Fluorophenyl)-1-[4-(methanesulfonyl)phenyl]prop-2-en-1-one
• 英文别名: 3-(4-fluorophenyl)-1-(4-methylsulfonylphenyl)prop-2-en-1-one
• CAS: 819792-59-1
• 化学式: C₁₆H₁₃FO₃S
• 分子量: 304.342
• InChiKey: WVUBWAMFOPCXMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-Fluorophenyl)-1-[4-(methanesulfonyl)phenyl]prop-2-en-1-one 在 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 生成 5-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)-1(4-sulfamoylphenyl)-1H-pyrazole
  参考文献：
  名称：

  Synthesis of novel halogenated triarylpyrazoles as selective COX-2 inhibitors: Anti-inflammatory activity, histopatholgical profile and in-silico studies

  摘要：

  A novel series of halogenated triarylpyrazoles 12a-l was designed and synthesized. All target compounds showed good in vitro COX-2 inhibitory activity (IC₅₀ = 0.043-0.17 µM) over COX-1 (IC₅₀ = 7.8 - 15.4 µM) relative to celecoxib (COX-1/IC₅₀ = 9.87, COX-2/IC₅₀ = 0.055), with acceptable selectivity index values (SI = 50.6-253.1). Also, they displayed moderate to potent in vivo anti-inflammatory activity (% edema inhibition = 16.9-87.9) comparable to celecoxib (% edema inhibition = 46.6-72.1) as standard drug. Three fluorinated pyrazoles 12a, 12g and 12j, exhibited superior anti-inflammatory activity at all time intervals (% edema inhibition = 42.1-87.9) with better gastric profile (UI = 1.25-2.5) than the traditional NSAID; indomethacin (UI = 14) and were close to the selective COX-2 inhibitor; celecoxib (UI = 1.75). In-silico docking and ADME studies of 12a, 12g and 12j supported the obtained biological data and pointed out their potential use for the development of bio-available, safe and potent anti-inflammatory drugs.

  DOI：

  10.1016/j.bioorg.2020.104418
• 作为产物：
  描述：

  4-甲砜基苯乙酮 、 对氟苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 10.0h， 生成 3-(4-Fluorophenyl)-1-[4-(methanesulfonyl)phenyl]prop-2-en-1-one
  参考文献：
  名称：

  新型 1,5-二芳基-3-[4-(甲基-磺酰基)苯基]-4,5-二氢-1H-吡唑衍生物作为潜在抗抑郁药的合成与评价

  摘要：

  为了开发有效的抗抑郁药，合成了新的吡唑啉衍生物 2a-s，并通过悬尾试验 (TST) 和改良的强迫游泳试验 (MFST) 评估了它们的抗抑郁样活性。还使用活动笼装置研究了化合物对自发运动活动的影响。在这些衍生物中，化合物 2b、2d、2f、2o 和 2r 降低了小鼠的水平和垂直活动次数。另一方面，化合物 2a、2h、2j、2k、2l、2m 和 2n 没有引起运动活性的任何显着变化，显着缩短了小鼠在 TST 和 MFST 中的不动时间，代表了抗抑郁样作用。此外，相同的化合物增加了小鼠在 MFST 中的游泳时间，而攀爬持续时间没有任何变化，类似于参考药物氟西汀 (10 mg/kg)。鉴于之前研究吡唑啉对中枢神经系统影响的论文，本研究再次指出吡唑啉衍生物具有显着的抗抑郁活性潜力。

  DOI：

  10.3390/molecules20022668

文献信息

• Synthesis and Evaluation of New 1,5-Diaryl-3-[4-(methyl-sulfonyl)phenyl]-4,5-dihydro-1H-pyrazole Derivatives as Potential Antidepressant Agents
  作者：Ahmet Özdemir、Mehlika Altıntop、Zafer Kaplancıklı、Özgür Can、Ümide Demir Özkay、Gülhan Turan-Zitouni

  DOI：10.3390/molecules20022668

  日期：——

  In an effort to develop potent antidepressant agents, new pyrazoline derivatives 2a–s were synthesized and evaluated for their antidepressant-like activity by tail suspension test (TST) and modified forced swimming test (MFST). The effects of the compounds on spontaneous locomotor activity were also investigated using an activity cage apparatus. Among these derivatives, compounds 2b, 2d, 2f, 2o, and

  为了开发有效的抗抑郁药，合成了新的吡唑啉衍生物 2a-s，并通过悬尾试验 (TST) 和改良的强迫游泳试验 (MFST) 评估了它们的抗抑郁样活性。还使用活动笼装置研究了化合物对自发运动活动的影响。在这些衍生物中，化合物 2b、2d、2f、2o 和 2r 降低了小鼠的水平和垂直活动次数。另一方面，化合物 2a、2h、2j、2k、2l、2m 和 2n 没有引起运动活性的任何显着变化，显着缩短了小鼠在 TST 和 MFST 中的不动时间，代表了抗抑郁样作用。此外，相同的化合物增加了小鼠在 MFST 中的游泳时间，而攀爬持续时间没有任何变化，类似于参考药物氟西汀 (10 mg/kg)。鉴于之前研究吡唑啉对中枢神经系统影响的论文，本研究再次指出吡唑啉衍生物具有显着的抗抑郁活性潜力。
• Antinociceptive Activities of Some 4,5-Dihydro-1H-Pyrazole Derivatives: Involvement of Central and Peripheral Pathways
  作者：Özgür Devrim Can、Feyza Alyu、Nazl| Turan、Ahmet Özdemir

  DOI：10.2174/1570180812666150819003950

  日期：2016.4.14

  This study was planned to investigate possible antinociceptive activity of 1,5-diaryl-3-[4- (methylsulfonyl)phenyl]-4,5-dihydro-1H-pyrazole derivatives (2a-s), based on the analgesia-inducing potential of 4,5-dihydro-1H-pyrazole moiety carrying compounds. Tail-clip and hot-plate tests, measuring centrally organized responses to a noxious stimulus, were performed in order to examine antinociceptive potential of the test compounds (100 mg/kg, i.p). In addition, peripherally mediated antinociceptive effect was evaluated by acetic acid-induced writhing tests. Motor coordination of the animals was tested in a Rota-rod apparatus. Among the tested compounds 2c, 2e, 2g, 2h, 2j, 2l, 2m, 2o and 2r prolonged the reaction time, measured in the tail-clip and hot-plate tests, with respect to the control values. The same compounds also decreased the quantity of acetic acidinduced writhing behaviours. In the Rota-rod tests, compound 2r was the only derivative decreasing the falling latency of mice. The obtained results indicated that some of the tested 4,5-dihydro-1H-pyrazole derivatives induce notable antinociceptive activity by effecting both of the central and peripheral nociceptive pathways. In addition, this study provided some information about structure-activity relationship for the compounds carrying similar chemical scaffold. Nevertheless, it should be noted that mechanism of action for these agents should be clarified with further detailed investigations.

  本研究计划根据携带 4,5-二氢-1H-吡唑分子的化合物的镇痛诱导潜力，研究 1,5-二芳基-3-[4-（甲基磺酰基）苯基]-4,5-二氢-1H-吡唑衍生物（2a-s）可能具有的抗痛觉活性。为了检测受试化合物（100 毫克/千克，静脉注射）的镇痛潜力，进行了夹尾试验和热板试验，以测量对有害刺激的中枢组织反应。此外，还通过醋酸引起的蠕动试验评估了外周介导的抗痛觉作用。与对照组相比，受试化合物中的 2c、2e、2g、2h、2j、2l、2m、2o 和 2r 延长了夹尾试验和热板试验的反应时间。这些化合物还减少了醋酸引起的蠕动行为。结果表明，一些受测的 4,5-二氢-1H-吡唑衍生物通过影响中枢和外周痛觉通路，诱导了显著的抗痛觉活性。此外，这项研究还为具有相似化学支架的化合物提供了一些有关结构-活性关系的信息。不过，应该指出的是，这些制剂的作用机制还需要进一步的详细研究才能明确。
• Synthesis and biological evaluation of N-substituted-3,5-diphenyl-2-pyrazoline derivatives as cyclooxygenase (COX-2) inhibitors
  作者：Rossella Fioravanti、Adriana Bolasco、Fedele Manna、Francesca Rossi、Francisco Orallo、Francesco Ortuso、Stefano Alcaro、Roberto Cirilli

  DOI：10.1016/j.ejmech.2010.10.005

  日期：2010.12

  Eighteen new 1-N-substituted-3,5-diphenyl-2-pyrazoline derivatives have been synthesized and cyclooxygenase (COX-1 and COX-2) inhibitory activities have been evaluated. The results of these biological assays showed that all of new derivatives are not endowed with improved anti-inflammatory activity against COX-1, but some of them showed a good activity against COX-2. To evaluate the binding mode of the most significative compounds (2d, 2f, 2g and 2k) docking studies were carried out. These studies confirmed biological data, in fact these compounds were able to fit into the active site of COX-2. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of novel triarylpyrazoline derivatives as selective COX-2 inhibitors
  作者：Khaled R.A. Abdellatif、Mohamed A. Abdelgawad、Madlen B. Labib、Taha H. Zidan

  DOI：10.1016/j.bmcl.2015.10.047

  日期：2015.12

  A new series of triarylpyrazoline derivatives 8a-p containing the most important COX-2 pharmacophore (SO2CH3 or/and SO2NH2) were synthesized by reaction of propen-1-one derivatives 6a-h with different phenyl hydrazine hydrochloride derivatives 7a-b in aqueous ethanol. All prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. All compounds were more selective for COX-2 isozyme than COX-1 isozyme and showed good in vivo anti-inflammatory activity. Compounds 8g, 8j and 8o showed the highest anti-inflammatory activity and were less ulcerogenic (Ulcer Index = 6.85, 7.7, 5.92, respectively) than indomethacin (Ulcer Index = 12.3) and comparable to celecoxib (Ulcer Index = 4.85). (C) 2015 Elsevier Ltd. All rights reserved.
• Synthesis of novel halogenated triarylpyrazoles as selective COX-2 inhibitors: Anti-inflammatory activity, histopatholgical profile and in-silico studies
  作者：Khaled R.A. Abdellatif、Eman K.A. Abdelall、Madlen B. Labib、Wael A.A. Fadaly、Taha H. Zidan

  DOI：10.1016/j.bioorg.2020.104418

  日期：2020.12

  A novel series of halogenated triarylpyrazoles 12a-l was designed and synthesized. All target compounds showed good in vitro COX-2 inhibitory activity (IC₅₀ = 0.043-0.17 µM) over COX-1 (IC₅₀ = 7.8 - 15.4 µM) relative to celecoxib (COX-1/IC₅₀ = 9.87, COX-2/IC₅₀ = 0.055), with acceptable selectivity index values (SI = 50.6-253.1). Also, they displayed moderate to potent in vivo anti-inflammatory activity (% edema inhibition = 16.9-87.9) comparable to celecoxib (% edema inhibition = 46.6-72.1) as standard drug. Three fluorinated pyrazoles 12a, 12g and 12j, exhibited superior anti-inflammatory activity at all time intervals (% edema inhibition = 42.1-87.9) with better gastric profile (UI = 1.25-2.5) than the traditional NSAID; indomethacin (UI = 14) and were close to the selective COX-2 inhibitor; celecoxib (UI = 1.75). In-silico docking and ADME studies of 12a, 12g and 12j supported the obtained biological data and pointed out their potential use for the development of bio-available, safe and potent anti-inflammatory drugs.