5-(5-chloro-2-hydroxyphenyl)-3-(4-fluorophenyl)-4,5-dihydropyrazole | 1049117-55-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 5-(5-chloro-2-hydroxyphenyl)-3-(4-fluorophenyl)-4,5-dihydropyrazole
• 英文别名: 4-chloro-2-[3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-5-yl]phenol
• CAS: 1049117-55-6
• 化学式: C₁₅H₁₂ClFN₂O
• 分子量: 290.724
• InChiKey: QDTKTHHQYHIFJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  44.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(5-chloro-2-hydroxyphenyl)-3-(4-fluorophenyl)-4,5-dihydropyrazole 在 4-二甲氨基吡啶 、 碳酸氢钠 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 10-chloro-2-(4-fluoro-phenyl)-1,11b-dihydro-pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one
  参考文献：
  名称：

  三环吡唑并[1,5- d ] [1,4]苯并x庚因-5（6H）-一个支架衍生物：选择性BuChE抑制剂的合成及生物学评价

  摘要：

  BuChE抑制剂在晚期阿尔茨海默氏病（AD）患者的治疗中起着重要作用。合成了一系列三环吡唑并[1,5- d ] [1,4]苯并x庚因-5（6H）-一衍生物，并将其评估为乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制剂。一些衍生物表现出选择性的BuChE抑制活性，这受三环支架的C6位取代基的体积和苯环上卤素取代基的体积的影响。其中，具有二卤素和6-乙基取代基的化合物3f和3o表现出最强的活性（IC 50分别 为2.95、2.04μM和对BuChE的混合型，非竞争性抑制）。Eutomer （6 R）-3o比（6 S）-3o表现出更好的BuChE抑制活性。化合物3o显示出无毒，良好的ADMET特性和显着的神经保护活性。对接研究揭示了靶酶活性位点内的相同结合方向。化合物3o通过三个氢键，一个烷基相互作用和三个Pi-烷基相互作用与BuChE很好地结合。选择性BuChE抑制剂在进行性神经退行性疾病中具有潜在用途。

  DOI：

  10.1016/j.ejmech.2018.02.002
• 作为产物：
  描述：

  4-氟苯乙酮 在 一水合肼 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 10.0h， 生成 5-(5-chloro-2-hydroxyphenyl)-3-(4-fluorophenyl)-4,5-dihydropyrazole
  参考文献：
  名称：

  三环吡唑并[1,5- d ] [1,4]苯并x庚因-5（6H）-一个支架衍生物：选择性BuChE抑制剂的合成及生物学评价

  摘要：

  BuChE抑制剂在晚期阿尔茨海默氏病（AD）患者的治疗中起着重要作用。合成了一系列三环吡唑并[1,5- d ] [1,4]苯并x庚因-5（6H）-一衍生物，并将其评估为乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制剂。一些衍生物表现出选择性的BuChE抑制活性，这受三环支架的C6位取代基的体积和苯环上卤素取代基的体积的影响。其中，具有二卤素和6-乙基取代基的化合物3f和3o表现出最强的活性（IC 50分别 为2.95、2.04μM和对BuChE的混合型，非竞争性抑制）。Eutomer （6 R）-3o比（6 S）-3o表现出更好的BuChE抑制活性。化合物3o显示出无毒，良好的ADMET特性和显着的神经保护活性。对接研究揭示了靶酶活性位点内的相同结合方向。化合物3o通过三个氢键，一个烷基相互作用和三个Pi-烷基相互作用与BuChE很好地结合。选择性BuChE抑制剂在进行性神经退行性疾病中具有潜在用途。

  DOI：

  10.1016/j.ejmech.2018.02.002

文献信息

• Novel tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one: Design, synthesis, model and use as hMAO-B inhibitors
  作者：Rui Chen、Jie Xiao、Yong Ni、Han-Fei Xu、Min Zheng、Xu Tong、Tong-Tian Zhang、Chenzhong Liao、Wen-Jian Tang

  DOI：10.1016/j.bmc.2016.02.045

  日期：2016.4

  hMAO-A inhibitors, on which, the intramolecular cyclization led to a very interesting change of isoform selectivity. A series of selective hMAO-B inhibitors (3a–3u) with novel scaffold of tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one were designed and synthesized. Compound 3u (IC50 = 221 nM) exhibited the best inhibitory activity and isoform selectivity against hMAO-B, superior to selegiline (IC50 = 321 nM)

  基于我们最近报道的选择性hMAO-A抑制剂，分子内环化作用导致异构体选择性发生了非常有趣的变化。设计并合成了一系列具有新型三环吡唑并[1,5- d ] [1,4]苯并恶嗪-5（6 H）-支架的选择性hMAO-B抑制剂（3a - 3u）。化合物3u（IC 50  = 221 nM）表现出最佳的抑制活性和对hMAO-B的同工型选择性，优于司来吉兰（IC 50 ＝ 321nM），其是用于帕金森氏病的商业选择性hMAO-B抑制剂。模型研究表明，我们的化合物对hMAO-B的选择性取决于至少两个残基，即Ile 199和Cys 172（或对应于hMAO-A的Phe 208和Asn 181）。这些数据支持进一步的研究，以评估更有效的选择性hMAO-B抑制剂的合理设计。
• Spiro Derivatives of 1,10b-dihydro-5H-pyrazolo[1,5-c][1,3]-benzoxazines and their Antimicrobial, Anti-Inflammatory, and Antioxidant Activity
  作者：Lidiya Z. Mandzyuk、Vasyl S. Matiychuk、Taras I. Chaban、Olesya V. Bodnarchuk、Julia E. Matiychuk、Mykola D. Obushak

  DOI：10.1007/s10593-020-02842-x

  日期：2020.11

  The reaction of 2-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)phenols with cyclopentanone, cyclohexanone, or 4-methylcyclohexanone gave spiro derivatives of 1,10b-dihydropyrazolo[1,5-c][1,3]benzoxazines. The antimicrobial, anti-inflammatory, and antioxidant activities of these compounds were studied. A compound with a high antimicrobial activity against S. aureus ATCC 43300, together with compounds possessing an anti-inflammatory effect superior to the reference drug diclofenac, as well as high antioxidant activity, were identified.

  2-(3-芳基-4,5-二氢-1H-吡唑-5-基)酚与环戊酮、环己酮或4-甲基环己酮的反应生成了1,10b-二氢吡唑[1,5-c][1,3]苯并噁嗪的螺旋衍生物。研究了这些化合物的抗菌、抗炎和抗氧化活性。鉴定出一种对金黄色葡萄球菌 ATCC 43300 具有高抗菌活性的化合物，以及一些抗炎效果优于参考药物双氟氯噻吨和具有高抗氧化活性的化合物。
• Design and synthesis of novel 2-pyrazoline-1-ethanone derivatives as selective MAO inhibitors
  作者：Xu Tong、Rui Chen、Tong-Tian Zhang、Yan Han、Wen-Jian Tang、Xin-Hua Liu

  DOI：10.1016/j.bmc.2014.12.010

  日期：2015.2

  Thirty seven novel 2-pyrazoline-1-ethanone derivatives were designed, synthesized and evaluated as selective hMAO inhibitors. Among them, compounds 7h (IC50 = 2.40 mu M) and 12c (IC50 = 2.00 mu M) exhibited best inhibitory activity and selectivity against hMAO-A, surpassing that of the positive control Clorgyline (IC50 = 2.76 mu M). Based on selective activity of hMAO-A, SAR analysis showed that the order of N1 substituent contribution was bromo (3) > piperidinyl (4) > morpholinyl (5) > imidazolyl (6), and compounds with electron-withdrawing substituents (-F, -Cl) at C3 or C5 phenyl ring of 2-pyrazoline nucleus dedicated stronger MAO-A inhibitory activity. Molecular docking showed that compounds 7h and 12c were nicely bound to hMAO-A via two hydrogen bonds (SER209, GLU216), one Pi-Pi interaction and three hydrogen bonds (SER209, GLU216, TYR69), one Sigma-Pi interaction, respectively. In addition, the substituent at C3 position of 2-pyrazoline with the N1 acetyl has little effect on MAO-A inhibitory activity. These data support further studies to assess rational design of more efficiently selective hMAO inhibitors in the future. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis, biological evaluation of novel 4,5-dihydro-2H-pyrazole 2-hydroxyphenyl derivatives as BRAF inhibitors
  作者：Jia-Jia Liu、Hui Zhang、Juan Sun、Zhong-Chang Wang、Yu-Shun Yang、Dong-Dong Li、Fei Zhang、Hai-Bin Gong、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2012.08.020

  日期：2012.10

  A series of novel 4,5-dihydropyrazole derivatives (3a-3t) containing hydroxyphenyl moiety as potential V600E mutant BRAF kinase (BRAF(V600E)) inhibitors were designed and synthesized. Docking simulation was performed to insert compounds 3d (1-(5-(5-chloro-2-hydroxyphenyl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone) and 3m (1-(3-(4-chlorophenyl)-5-(3,5-dibromo-2-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone) into the crystal structure of BRAF(V600E) to determine the probable binding model, respectively. Based on the preliminary results, compound 3d and 3m with potent inhibitory activity in tumor growth may be a potential anticancer agent. Results of the bioassays against BRAF(V600E), MCF-7 human breast cancer cell line and WM266.4 human melanoma cell line all showed several compounds had potent activities IC50 value in low micromolar range, among them, compound 3d and compound 3m showed strong potent anticancer activity, which were proved by that 3d: IC50 = 1.31 mu M for MCF-7 and IC50 = 0.45 mu M for WM266.5, IC50 = 0.22 mu M for BRAF(V600E), 3m: IC50 = 0.97 mu M for MCF-7 and IC50 = 0.72 mu M for WM266.5, IC50 = 0.46 mu M for BRAF(V600E), which were comparable with the positive control Erlotinib. (C) 2012 Elsevier Ltd. All rights reserved.
• Tricyclic pyrazolo[1,5- d ][1,4]benzoxazepin-5(6H)-one scaffold derivatives: Synthesis and biological evaluation as selective BuChE inhibitors
  作者：Shi-Chao Chen、Guo-Liang Qiu、Bo Li、Jing-Bo Shi、Xin-Hua Liu、Wen-Jian Tang

  DOI：10.1016/j.ejmech.2018.02.002

  日期：2018.3

  roles in treatment of patients with advanced Alzheimer's disease (AD). A series of tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one derivatives were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Some derivatives showed selective BuChE inhibitory activity, which was influenced by the volumes of the substituted groups at the C6 position and

  BuChE抑制剂在晚期阿尔茨海默氏病（AD）患者的治疗中起着重要作用。合成了一系列三环吡唑并[1,5- d ] [1,4]苯并x庚因-5（6H）-一衍生物，并将其评估为乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）抑制剂。一些衍生物表现出选择性的BuChE抑制活性，这受三环支架的C6位取代基的体积和苯环上卤素取代基的体积的影响。其中，具有二卤素和6-乙基取代基的化合物3f和3o表现出最强的活性（IC 50分别 为2.95、2.04μM和对BuChE的混合型，非竞争性抑制）。Eutomer （6 R）-3o比（6 S）-3o表现出更好的BuChE抑制活性。化合物3o显示出无毒，良好的ADMET特性和显着的神经保护活性。对接研究揭示了靶酶活性位点内的相同结合方向。化合物3o通过三个氢键，一个烷基相互作用和三个Pi-烷基相互作用与BuChE很好地结合。选择性BuChE抑制剂在进行性神经退行性疾病中具有潜在用途。