5-(2-hydroxyphenyl)pyrazoline | 99068-00-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 5-(2-hydroxyphenyl)pyrazoline
• 英文别名: 3-Methyl-5-(2-hydroxyphenyl)-pyrazolin；2-(3-methyl-4,5-dihydro-1H-pyrazol-5-yl)phenol；2-(5-methyl-3,4-dihydro-2H-pyrazol-3-yl)-phenol
• CAS: 99068-00-5
• 化学式: C₁₀H₁₂N₂O
• 分子量: 176.218
• InChiKey: XAVAGKOVTZLSSJ-UHFFFAOYSA-N

物化性质

• 熔点：
  105-106 °C
• 沸点：
  264.0±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  44.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(2-hydroxyphenyl)pyrazoline 在 4-二甲氨基吡啶 、 potassium iodide 作用下， 以 丙酮 为溶剂， 反应 6.0h， 生成 1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl)-2-(4-hydroxypiperidin-1-yl)ethanone
  参考文献：
  名称：

  Design and synthesis of novel 5-phenyl-N-piperidine ethanone containing 4,5-dihydropyrazole derivatives as potential antitumor agents

  摘要：

  A series of novel 5-phenyl-N-piperidine ethanone-4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassays demonstrated that compounds 4d, 4f, 7a and 7h occupied high antiproliferative activities against SGC-7901, MGC-803 and Bcap-37 cell lines. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 7b showed the most potent inhibitory activity with IC50 value at 2.00 +/- 0.40 mu M. The active compound 4d was also docked into the telomerase TERT active site to determine the probable binding model. The results indicated that conserved residues Lys189, Asp254 and Gln308 were important for ligand binding via hydrogen bond interactions. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.02.040
• 作为产物：
  描述：

  4-(2-hydroxyphenyl)but-3-en-2-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 5-(2-hydroxyphenyl)pyrazoline
  参考文献：
  名称：

  三环吡唑并[1,5-c] [1,3]苯并恶嗪-5（5H）-1骨架作为BuChE选择性抑制剂的设计，合成及生物学评价。

  摘要：

  基于三环支架作为丁酰胆碱酯酶（BuChE）抑制剂的结构分析，设计，合成了一系列吡唑并[1,5-c] [1,3]苯并恶嗪-5（5H）-one衍生物，并对其乙酰胆碱酯酶进行了评估（ AChE）和BuChE抑制活性。具有5-羰基和7-或/和9-卤素取代基的化合物显示出潜在的BuChE抑制活性，其中化合物6a，6c和6g显示出最佳的BuChE抑制作用（IC50分别为1.06、1.63和1.63 µM）。结构活性关系表明5-羰基和卤素取代基显着影响BuChE活性。发现化合物6a和6g无毒，亲脂并显示出显着的神经保护活性和对BuChE的混合型抑制作用（Ki分别为7.46和3.09 µM）。

  DOI：

  10.1080/14756366.2018.1488696

文献信息

• 一种三环吡唑[1,5-c][1,3]苯并噁嗪酮衍生 物及其制备方法与用途
  申请人：安徽医科大学

  公开号：CN108299464B

  公开（公告）日：2020-07-07

  本发明公开了一种三环吡唑[1,5‑c][1,3]苯并噁嗪酮衍生物，其结构如下列通式Ⅰ所示：其中R1为卤素、C1‑C6‑烷基或C1‑C6‑烷氧基；R2为卤素、C1‑C6‑烷基或C1‑C6‑烷氧基；R3为卤素、C1‑C6‑烷基或C1‑C6‑烷氧基；R4为卤素、C1‑C6‑烷基或C1‑C6‑烷氧基。本发明提供的是一种可逆、选择性的BuChE抑制剂，具有良好的胆碱酯酶抑制活性，且对BuChE抑制活性具有选择性；其中部分优选的三环吡唑[1,5‑c][1,3]苯并噁嗪酮衍生物具有较好的BuChE抑制活性，部分三环吡唑[1,5‑c][1,3]苯并噁嗪酮衍生物的BuChE抑制活性优于阳性对照药donepezil。
• Synthesis of some pyrazolo[1,5-<i>c</i>][1,3]benzoxazines and a new 5<i>H</i>-pyrazolo[1,5-c][1,3,2]benzoxazaphosphorine ring system
  作者：Jan Svetlik、Nada Pronayova、Jiri Kubista

  DOI：10.1002/jhet.5570420616

  日期：2005.9

  N-carbonyldiimidazole leading to pyrazolobenzoxazine derivatives were studied. The observed diastere-oselectivity is discussed. Reaction of 3a with Lawesson reagent gave rise to a new 5H-pyrazolo[1,5-c]-[1,3,2]benzoxazaphosphorine heterocyclic system.

  研究了5-（2-羟苯基）吡唑啉3a与4-羧基苯甲醛，乙醛酸和N，N-羰基二咪唑的缩合反应生成吡唑并苯并恶嗪衍生物。讨论了观察到的非对映选择性。的反应图3a与Lawesson试剂产生了一个新的5 ħ -吡唑并[1,5-C] - [1,3,2] benzoxazaphosphorine杂环体系。
• Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo
  作者：Yang Wang、Fei Xiong Cheng、Xiao Long Yuan、Wen Jian Tang、Jing Bo Shi、Chen Zhong Liao、Xin Hua Liu

  DOI：10.1016/j.ejmech.2016.02.009

  日期：2016.4

  It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. In order to carry out more rational design, based on structure-based drug design, several series of N-substituted-dihydropyrazole derivatives, totally 78 compounds as potential human telomerase inhibitors were designed and synthesized. The results demonstrated that some compounds had potent anticancer activity against four tumor cell lines, and showed good selectivity on tumor cells over somatic cells. By the modified TRAP assay, compound 13i exhibited the most potent inhibitory activity against telomerase with an IC50 value of 0.98 mu M. In vivo evaluation results indicated that compound 13i could inhibit growth of S180 and HepG2 tumor-bearing mice, and it also significantly enhanced the survival rate of EAC tumor-bearing mice. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. These data support further studies to assess rational design of more efficient telomerase inhibitors in the future. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Design and synthesis of novel 2-methyl-4,5-substitutedbenzo[f]-3,3a,4,5-tetrahydro-pyrazolo[1,5-d][1,4]oxazepin-8(7H)-one derivatives as telomerase inhibitors
  作者：Xin-Hua Liu、Ying-Ming Jia、Bao-An Song、Zhi-xiang Pang、Song Yang

  DOI：10.1016/j.bmcl.2012.11.101

  日期：2013.2

  Eight novel 4,5-tetrahydropyrazolo[1,5-d][1,4] oxazepine derivatives have been synthesized and purified to be screened for anticancer activity. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 4a showed the most potent inhibitory activity with IC50 value at 0.78 +/- 0.22 mu M. Western blot assays showed that compounds 4a and 4b could inhibit expression of Cyclin D1, TERT, phospho-AKT and PI3K/AKT pathway. (c) 2012 Elsevier Ltd. All rights reserved.
• Identification of human telomerase inhibitors having the core of N -acyl-4,5-dihydropyrazole with anticancer effects
  作者：Xuan Xiao、Yong Ni、Ying-Ming Jia、Min Zheng、Han-Fei Xu、Jun Xu、Chenzhong Liao

  DOI：10.1016/j.bmcl.2016.02.025

  日期：2016.3

  Eight human telomerase inhibitors (5a-5h) having the core of N-acyl-4,5-dihydropyrazole with anticancer effects were identified in this study. Biological results revealed that a few compounds had potent anticancer activities against three common tumor cell lines (SGC-7901, HepG2 and MGC-803). Among them, compound 5c, with a molecular weight of only 272.2 Da, had antiproliferative activities against SGC-7901 and MGC-803 with EC50 values of 2.06 +/- 0.17 and 2.89 +/- 0.62 mu M, respectively, better than 5-Fluorouracil. Compound 5c inhibited the enzyme of telomerase with an IC50 value of 1.86 +/- 0.51 mu M, surpassing the control compound, ethidium bromide. Modeling study showed that this compound can reside in the binding pocket of the telomerase/TNA: DNA hairpin complex. When the moiety of N-acyl was changed to N-sulfonyl, the gotten compounds (8a-8i) had deteriorative activities against both these three cancer cell lines and the enzyme of telomerase. (C) 2016 Elsevier Ltd. All rights reserved.