3-(4-methoxyphenyl)-5-(4-chlorophenyl)-2-pyrazoline | 75745-48-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(4-methoxyphenyl)-5-(4-chlorophenyl)-2-pyrazoline
• 英文别名: 5-(4-chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole
• CAS: 75745-48-1
• 化学式: C₁₆H₁₅ClN₂O
• 分子量: 286.761
• InChiKey: FJNKXTXTYNUEIK-UHFFFAOYSA-N

物化性质

• 熔点：
  152-155 °C(Solv: ethanol (64-17-5))
• 沸点：
  428.1±55.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 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：
  33.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-methoxyphenyl)-5-(4-chlorophenyl)-2-pyrazoline 在 sodium nitrite 作用下， 以 盐酸 为溶剂， 以73%的产率得到3-(4-chlorophenyl)-5-(4-methoxyphenyl)-2-nitroso-3,4-dihydropyrazole
  参考文献：
  名称：

  Sayed, G. H., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 5, p. 364 - 367

  摘要：

  DOI：
• 作为产物：
  描述：

  4'-methoxy-4-chlorochalcone 在 一水合肼 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以94%的产率得到3-(4-methoxyphenyl)-5-(4-chlorophenyl)-2-pyrazoline
  参考文献：
  名称：

  Exploration of the SAR of anti-invasive chalcones: Synthesis and biological evaluation of conformationally restricted analogues

  摘要：

  In order to get a clearer view on the active geometry of anti-invasive chalcones, we have prepared a number of isoxazoles and related substances as conformationally restrained mimics of 1,3-diarylpropenones, and also of (Z)-stilbenes. In vitro anti-invasive activity data for 3,5-isoxazoles and 4,5-isoxazoles, together with an in silico geometrical comparison, point towards an active conformation for chalcones more resembling their s-trans geometry than the s-cis counterpart. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.069

文献信息

• Discovery and Pharmacophore Studies of Novel Pyrazole-Based Anti-Melanoma Agents
  作者：Qing-Shan Li、Xian-Hai Lü、Yang Yang、Ban-Feng Ruan、Ri-Sheng Yao、Chen-Zhong Liao

  DOI：10.1002/cbdv.201400143

  日期：2015.1

  urgently needed. Several recent developments indicate that the V600E mutant BRAF (BRAFV600E) is a validated target for antimelanoma‐drug development. Based on in silico screening results, a series of novel pyrazole derivatives has been designed, synthesized, and evaluated in vitro for their inhibitory activities against BRAFV600E melanoma cells. Compound 3d exhibited the most potent inhibitory activity

  由于发病率不断上升且缺乏有效的治疗方法，恶性黑色素瘤是最危险的皮肤癌形式，因此迫切需要新的治疗策略。最近的几项进展表明，V600E 突变体 BRAF（BRAFV600E）是抗黑色素瘤药物开发的有效靶点。基于计算机筛选结果，设计、合成了一系列新型吡唑衍生物，并在体外评估了它们对 BRAFV600E 黑色素瘤细胞的抑制活性。化合物 3d 表现出最有效的抑制活性，对 BRAFV600E 的 IC50 值为 0.63 μM，对突变型 BRAF 依赖性细胞的 GI50 值为 0.61 μM。此外，QSAR 建模和抑制剂类似物的对接模拟为进一步的结构优化提供了重要的药效团线索。
• Synthesis of New 4-Thiazolidinone-, Pyrazoline-, and Isatin-Based Conjugates with Promising Antitumor Activity
  作者：Dmytro Havrylyuk、Borys Zimenkovsky、Olexandr Vasylenko、Andrzej Gzella、Roman Lesyk

  DOI：10.1021/jm300789g

  日期：2012.10.25

  The synthesis and antitumor activity screening of novel 3-[2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-4-oxo-4,5-dihydro-1,3-thiazol-5-ylidene]-2,3-dihydro-1H-indol-2-ones 1–23 and 3-(3,5-diarylpyrazol-1-yl)-2,3-dihydro-1H-indol-2-ones 24–39 are performed. In vitro anticancer activity of the synthesized compounds was tested by the National Cancer Institute. Most of them displayed anticancer activity on leukemia

  新型3- [2-（3,5-二芳基-4,5-二氢吡唑-1-基）-4-氧代-4,5-二氢-1,3-噻唑-5-亚烷基的合成及抗肿瘤活性的筛选] -2,3-dihydro-1 H-吲哚-2-ones 1 – 23和3-（3,5-diarylpyrazol-1-yl）-2,3-dihydro-1 H -indol-2-ones 24 –执行39次。美国国家癌症研究所测试了合成化合物的体外抗癌活性。他们中的大多数对白血病，黑素瘤，肺癌，结肠癌，中枢神经系统，卵巢癌，肾癌，前列腺癌和乳腺癌细胞系均表现出抗癌活性。讨论了构效关系。发现最有效的抗癌化合物10具有平均GI 50的活性TGI值分别为0.071μM和0.76μM。它显示出对非小细胞肺癌细胞HOP-92（GI 50 <0.01μM），结肠癌细胞系HCT-116（GI 50 = 0.018μM），CNS癌细胞SNB-75（ GI 50 = 0.0159μM），卵巢癌细胞系NCI
• Synthesis and Anticancer Activity of Isatin-Based Pyrazolines and Thiazolidines Conjugates
  作者：Dmytro Havrylyuk、Natalya Kovach、Borys Zimenkovsky、Olexandr Vasylenko、Roman Lesyk

  DOI：10.1002/ardp.201100055

  日期：2011.8

  The synthesis and antitumor activity screening of novel isatin based conjugates with thiazolidine and pyrazoline moieties were performed. Reaction of 3,5‐diaryl‐4,5‐dihydropyrazoles with chloroacetyl chloride yielded starting 2‐chloro‐1‐(3,5‐diaryl‐4,5‐dihydropyrazol‐1‐yl)‐ethanones which were utilized in alkylation of isatin and 5‐bromoisatin. Thus, corresponding 1‐[2‐(3,5‐diaryl‐4,5‐dihydropyraz

  进行了具有噻唑烷和吡唑啉部分的新型靛红基缀合物的合成和抗肿瘤活性筛选。3,5-二芳基-4,5-二氢吡唑与氯乙酰氯反应生成起始的2-氯-1-（3,5-二芳基-4,5-二氢吡唑-1-基）-乙酮，用于靛红的烷基化和 5-溴皂苷。因此，得到了相应的1-[2-(3,5-二芳基-4,5-二氢吡唑-1-基)-2-氧乙基]-1H-吲哚-2,3-二酮(1a-1d)。化合物 1a-1d 已用于与 4-噻唑烷酮的 Knoevenagel 缩合反应，得到一系列 5-亚苯基衍生物 2a-2f 和 3a-3d。测试合成的化合物在 NCI60 细胞系中的抗癌活性。被测化合物中，5-溴-1-2-[5-(4-氯苯基)-3-(4-甲氧基苯基)-4,5-二氢吡唑-1-基]-2-氧乙基}-1H-吲哚-2,
• Kinetic study of the homolytic brominolysis of 1,2-diarylcyclopropanes
  作者：Douglas E. Applequist、Rick D. Gdanski

  DOI：10.1021/jo00325a014

  日期：1981.6
• Synthesis, biological evaluation and 3D-QSAR studies of novel 4,5-dihydro-1H-pyrazole niacinamide derivatives as BRAF inhibitors
  作者：Cui-Yun Li、Qing-Shan Li、Li Yan、Xiao-Guang Sun、Ran Wei、Hai-Bin Gong、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2012.04.047

  日期：2012.6

  A series of novel 4,5-dihydropyrazole derivatives containing niacinamide moiety as potential V600E mutant BRAF kinase (BRAF(V600E)) inhibitors were designed and synthesized. Results of the bioassays against BRAF(V600E) and WM266.4 human melanoma cell line showed several compounds to be endowed potent activities with IC50 and GI(50) value in low micromolar range, among which compound 27e, (5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)6-methylpyridin-3-yl methanone (IC50 = 0.20 mu M, GI(50) = 0.89 mu M) was bearing the best bioactivity comparable with the positive control Sorafenib. Docking simulation was performed to determine the probable binding model and 3D-QSAR model was built to provide more pharmacophore understanding that could use to design new agents with more potent BRAF(V600E) inhibitory activity. (C) 2012 Published by Elsevier Ltd.