4-Chloro-2-[5-(4-methoxy-phenyl)-3,4-dihydro-2H-pyrazol-3-yl]-phenol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-Chloro-2-[5-(4-methoxy-phenyl)-3,4-dihydro-2H-pyrazol-3-yl]-phenol
• 英文别名: 4-chloro-2-[3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-5-yl]phenol
• 化学式: C₁₆H₁₅ClN₂O₂
• 分子量: 302.76
• InChiKey: BEYRXDAXFPIQOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  53.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-Chloro-2-[5-(4-methoxy-phenyl)-3,4-dihydro-2H-pyrazol-3-yl]-phenol 在 4-二甲氨基吡啶 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 1-(5-(5-chloro-2-hydroxy-phenyl)-3-(4-methoxy-phenyl)-4,5-dihydro-pyrazol-1-yl)ethanone-2-piperidine
  参考文献：
  名称：

  Design and synthesis of novel 2-pyrazoline-1-ethanone derivatives as selective MAO inhibitors

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2014.12.010
• 作为产物：
  描述：

  (E)-1-(5-chloro-2-hydroxyphenyl)-3-(4-methoxyphenyl)-prop-2-en-1-one 在 盐酸肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以69%的产率得到4-Chloro-2-[5-(4-methoxy-phenyl)-3,4-dihydro-2H-pyrazol-3-yl]-phenol
  参考文献：
  名称：

  2'-羟基-5'-氯查耳酮及其衍生物合成Δ2-吡唑啉异构体

  摘要：

  摘要 在回流的 DMF 中用盐酸肼适当取代 2'-羟基-5'-氯查耳酮得到异构体 Δ2-吡唑啉，并根据化学和光谱数据对其进行表征。

  DOI：

  10.1080/00397910008086963

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。
• 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.