1-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-ol | 854678-00-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-ol
• 英文别名: 1‐(4‐fluorophenyl)‐3‐(trifluoromethyl)‐1H‐pyrazol‐5‐ol
• CAS: 854678-00-5
• 化学式: C₁₀H₆F₄N₂O
• mdl: MFCD08719440
• 分子量: 246.164
• InChiKey: AAQODJKYJVPXLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  38.05
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-ol 在 palladium(II) trifluoroacetate 、 氢气 、 (R)-(+)-(6,6′-二甲氧联苯-2,2′-二基)双(二苯基膦) 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 60.0 ℃ 、8.27 MPa 条件下， 反应 48.0h， 以93%的产率得到(5S)-2-(4-fluorophenyl)-5-(trifluoromethyl)pyrazolidin-3-one
  参考文献：
  名称：

  Pd-catalyzed asymmetric hydrogenation of fluorinated aromatic pyrazol-5-ols via capture of active tautomers

  摘要：

  在这里，我们探索了一种新颖的策略，通过捕获活性互变异构体，对芳香性吡唑-5-醇进行不对称氢化。

  DOI：

  10.1039/c5sc00835b
• 作为产物：
  描述：

  4-氟苯肼盐酸盐 、 三氟乙酰乙酸乙酯 以 乙醇 为溶剂， 反应 8.0h， 以83%的产率得到1-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-ol
  参考文献：
  名称：

  F（1H-吡唑-4-基）亚甲基-肼化物衍生物：合成和抗菌活性

  摘要：

  本文考虑了各种支撑设计参数和SMA极限状态的影响，研究了形状记忆合金（SMA）支撑钢框架结构的抗震和倒塌性能。SMA支撑钢框架建筑的设计强度和刚度可与案例研究建筑所选择的抗钢矩框架相媲美。然后，系统地改变了最初设计的参考SMA支撑框架中SMA支撑的刚度和最终变形能力。首先，采用静力推覆分析和增量动态分析（IDA）来说明SMA支撑失效考虑因素在具有SMA元素的钢框架抗震性能评估中的重要性。然后，通过推覆分析，非线性响应历史分析和IDA研究了SMA支撑初始刚度和最终变形能力对SMA支撑框架的抗震和倒塌性能的影响。结果表明，在设计和最大考虑地震（MCE）级地震危险或框架倒塌能力时，SMA支撑的初始刚度不会影响层间位移和地板的绝对加速度响应。但是，它对框架的事后功能有相当大的影响。还发现，SMA支撑的极限变形能力应至少为MCE级别最大层间漂移需求的80％，以获得令人满意的抗震性能，而较大的值可为SMA支撑框架提供更高的坍塌能力。

  DOI：

  10.1002/jhet.3816

文献信息

• Synthesis of Isoxazole, 1, 2, 4-Oxadiazole and (1<i>H</i>-Pyrazol-4-yl)-methanone Oxime Derivatives from<i>N</i>-Hydroxy-1<i>H</i>-pyrazole-4-carbimidoyl Chloride and their Biological Activity
  作者：Bhavanarushi Sangepu、Bharath Gandu、Gangagnirao Anupoju、Vatsalarani Jetti

  DOI：10.1002/jhet.2309

  日期：2016.5

  Some novel isoxazole‐, 1,2,4 oxadiazole‐, and (1H‐pyrazol‐4‐yl)‐methanone oxime derivatives were synthesized from N‐hydroxy‐1H‐pyrazole‐4‐carbimidoyl chloride and the structures of all products were identified by spectral data (1H‐NMR, 13C‐NMR, IR, MS, and HRMS) and evaluated their antibacterial activity.

  从N-羟基-1 H-吡唑-4-碳亚氨基酰氯和一些产品的结构合成了一些新颖的异恶唑，1,2,4恶二唑和（1 H-吡唑-4-基）甲酮肟衍生物通过光谱数据（1 H-NMR，13 C-NMR，IR，MS和HRMS）鉴定并评估其抗菌活性。
• One‐Pot Two‐Step Synthesis of Isochromene‐Fused CF ₃ ‐Substituted Pyrazoles
  作者：Andrea M. Nikolić、Filip Živković、Života Selaković、Peter Wipf、Igor M. Opsenica

  DOI：10.1002/ejoc.202000942

  日期：2020.9.14

  An efficient one‐pot, two step method for fusing two biologically active motifs, CF3‐substituted pyrazoles and isochromenes, was developed. Selective O‐benzylation of CF3‐substituted pyrazolones and subsequent Pd‐catalyzed direct C–H arylation generate a fused tricycle.

  开发了一种有效的一锅两步方法，用于融合两个生物活性基序CF 3取代的吡唑和异色酮。CF 3取代的吡唑啉酮的选择性O-苄基化反应以及随后的Pd催化的直接C–H芳基化反应生成一个稠合的三环。
• 5‐Alkoxy‐1‐aryl‐3‐polyfluoroalkylpyrazoles with Antinociceptive Activity: Partial Agonists of TRPV1 Ion Channels
  作者：Olga G. Khudina、Yanina V. Burgart、Natalia A. Malkova、Evgeny V. Shchegolkov、Olga P. Krasnykh、Galina A. Triandafilova、Ksenia O. Malysheva、Sergey Yu. Solodnikov、Elisaveta S. Dubodel、Yuliya V. Korolkova、Sergey A. Kozlov、Sophia S. Borisevich、Evgenii S. Mozhaitsev、Victor I. Saloutin

  DOI：10.1002/cmdc.202300063

  日期：2023.6.15

  Chemoselective O‐alkylation of 1‐aryl‐3‐polyfluoroalkylpyrazol‐5‐oles under basic conditions resulted in a series of 5‐alkoxypyrazoles (26 derivatives). They showed an acceptable ADME profile (in silico) and can be considered as drug‐like. In experiments in vivo (CD‐1 mice), it was found that the obtained compounds do not have toxic properties at a dose of more than 150 mg/kg (for most compounds at a dose of >300 mg/kg, and for lead compounds – >600 mg/kg). 22 Compounds from this series demonstrated from moderate to high analgesic effects (28–104 % at 1 h and 37–109 % at 2 h after administration) in vivo in the hot plate test (SD rats, 15 mg/kg, intraperitoneal (ip)). The lead compound was 4‐([1‐phenyl‐3‐(trifluoromethyl)pyrazol‐5‐yl]oxy)butan‐1‐ol, which not only increased the latent period in the hot plate test by 103 % at both measurement points but also showed a pronounced analgesic effect under conditions of capsaicin‐induced nociception (CD‐1 mice, 15 mg/kg, ip). According to molecular modeling, all synthesized compounds can interact with the TRPV1 ion channel. This biological target was confirmed in in vitro experiments on Chinese hamster ovary cells expressing rTRPV1. 5‐Alkoxypyrazoles were partial agonists of the TRPV1 ion channel in various degree, and the most active was the same pyrazole as in in vivo tests.

  摘要在碱性条件下对 1-芳基-3-聚氟烷基吡唑-5-醇进行化学选择性 O-烷基化反应，产生了一系列 5-烷氧基吡唑（26 种衍生物）。这些衍生物显示出可接受的 ADME 特征（在硅学中），可被视为类药物。在体内（CD-1 小鼠）实验中发现，获得的化合物在剂量超过 150 毫克/千克时不会产生毒性（大多数化合物的剂量为 300 毫克/千克，主要化合物的剂量为 600 毫克/千克）。22 在热板试验（SD 大鼠，15 毫克/千克，腹腔注射 (ip)）中，该系列化合物显示出中等到较高的镇痛效果（给药后 1 小时为 28-104%，2 小时为 37-109%）。领头化合物是 4-([1-苯基-3-(三氟甲基)吡唑-5-基]氧基)丁-1-醇，它不仅使热板试验的潜伏期在两个测量点都延长了 103%，而且在辣椒素诱导的痛觉条件下（CD-1 小鼠，15 毫克/千克，ip）显示出明显的镇痛效果。根据分子模型，所有合成化合物都能与 TRPV1 离子通道相互作用。在表达 rTRPV1 的中国仓鼠卵巢细胞上进行的体外实验证实了这一生物靶点。5-烷氧基吡唑在不同程度上是 TRPV1 离子通道的部分激动剂，其中活性最强的是与体内试验相同的吡唑。
• Synthesis and antibacterial activity of 4,4′-(aryl or alkyl methylene)-bis(1H-pyrazol-5-ol) derivatives
  作者：S. Bhavanarushi、V. Kanakaiah、Gandu Bharath、A. Gangagnirao、J. Vatsala Rani

  DOI：10.1007/s00044-013-0623-3

  日期：2014.1

  A rapid, improved, and environmentally benign synthesis of 4,4'-aryl or alkyl methylene-bis(1H-pyrazol-5-ols) has been accomplished by tandem Knoevenagel-Michael reaction of 1-aryl-3-alkyl-1H-pyrazol-5-ol with various aldehydes catalyzed by ammonium acetate. All the synthesized compounds 3a-v were evaluated in vitro for their antibacterial activity against Pseudomonas aeruginosa, Xanthomonas protophormiae, Bacillus licheniformis, and Staphylococcus aureus. Among the tested compounds, compounds with trifluromethyl group show excellent antibacterial activity.
• Synthesis, cytotoxic, and DNA binding studies of novel fluorinated condensed pyrano pyrazoles
  作者：S. Bhavanarushi、V. Kanakaiah、E. Yakaiah、V. Saddanapu、A. Addlagatta、J. Vatsala Rani

  DOI：10.1007/s00044-012-0239-z

  日期：2013.5

  One pot solvent-free synthetic method is developed for the synthesis of novel pyrano[2,3-c]pyrazole analogs. Cytotoxicity experiments conducted against a pair of cancerous, non-cancerous lung cell lines, and a cervical cell line is described. These compounds are selectively toxic against cancer cells and not normal cells. Molecular mechanism is established for the mode of DNA binding of these compounds using electrochemical and proton NMR methods.