2-(5-(2,3-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-1-ol

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(5-(2,3-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-1-ol
• 英文别名: 2-[5-(2,3-dimethoxyphenyl)-pyrazolin-3-yl]naphthalen-1-ol；2-[5-(2,3-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl]naphthalen-1-ol
• 化学式: C₂₁H₂₀N₂O₃
• 分子量: 348.401
• InChiKey: WLFUBRZSKYOQLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  63.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(5-(2,3-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-1-ol 、 异氰酸2-甲氧苯酯 以 乙醇 为溶剂， 以80%的产率得到3-(1-hydroxynaphthalen-2-yl)-5-(2,3-dimethoxyphenyl)-N-(2-methoxyphenyl)-pyrazoline-1-carbothioamide
  参考文献：
  名称：

  Anticancer and structure-activity relationship evaluation of 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide analogs of chalcone

  摘要：

  To identify new potent chemotherapeutic agents, we synthesized compounds with 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide (NDPC) skeletons and evaluated their cytotoxicities using a clonogenic long-term survival assay. Their half-maximal cell growth inhibitory concentrations ranged from a few hundred nanomolars to a few micromolars. Further biological experiments including flow cytometry and western blotting analysis were performed with the derivative showing the best cytotoxicity. To identify a target protein of the selected compound, an in vitro kinase assay was carried out, which revealed that aurora kinases A and B were inhibited by the test compound, and this was confirmed using western blot analysis. The molecular binding mode between the selected compound and the kinases was elucidated using in silico docking. The structural conditions required for good cytotoxicity were identified based on the quantitative relationships between the physicochemical properties of the derivatives and their cytotoxicities. (C) 2016 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2016.08.003
• 作为产物：
  描述：

  3-(2,3-Dimethoxyphenyl)-1-(1-hydroxynaphthalen-2-yl)prop-2-en-1-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以86%的产率得到2-(5-(2,3-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-1-ol
  参考文献：
  名称：

  Synthetic Naphthoflavonoids Showing Inhibitory Effects on Clonogenicity against Cisplatin-Resistant A2780/Cis Human Ovarian Cancer Cells

  摘要：

  早期卵巢癌的检测难度较大，而卵巢癌是女性癌症相关死亡的第四大原因，因此需要开发新型化疗药物。由于几种类黄酮显示出对卵巢癌的抗癌活性，本研究设计并合成了35种萘基类黄酮，包括3',4'-萘酮酮、5',6'-萘酮、7,8-萘黄酮、5,6-萘黄烷酮、5,6-萘黄酮、2,3-萘酮、N-苯基吡唑基-5',6'-萘酮、碳硫酰胺吡唑基-5',6'-萘酮、吡唑基-3',4'-萘酮及碳硫酰胺吡唑基-3',4'-萘酮。为了探索这些化합物的抗癌效果，采用了克隆形成长期存活实验，对人类顺铂耐药的A2780/Cis卵巢癌细胞进行实验。使用比较分子场分析和全息量化结构-活性关系探讨了35种萘基类黄酮的结构特性与它们的克隆形成能力之间的关系。结果表明，识别出几种可以增强细胞生长抑制活性的结构特征，进一步设计并合成了满足这些条件的化合物5-(2,3-二甲氧基苯基)-3-(1-羟基萘-2-基)-N-苯基-4,5-二氢-1H-吡唑-1-碳硫酰胺。该新型化合物的半最大细胞生长抑制浓度低于本文测试的35种类黄酮衍生物。因此，本报告中观察到的结构特征可用于设计和开发有效的化疗药物以治疗卵巢癌细胞。

  DOI：

  10.2174/1570180812666150213230949

文献信息

• Complete assignments of ¹ H and ¹³ C NMR data for 21 naphthalenyl-phenyl-pyrazoline derivatives
  作者：Doseok Hwang、Hyuk Yoon、Seunghyun Ahn、Dong-Wook Kim、Dong-Ho Bae、Dongsoo Koh、Yoongho Lim

  DOI：10.1002/mrc.3981

  日期：2013.9

  To find potent new chemotherapy drugs, we designed and synthesized a series of naphthochalcones bearing naphthalenyl‐phenyl‐pyrazoline moieties. The complete 1H and 13C NMR data for these compounds are reported here and can be used to identify further new naphthochalcones bearing the desired pyrazoline moieties. Copyright © 2013 John Wiley & Sons, Ltd.

  为了寻找有效的新化疗药物，我们设计并合成了一系列带有萘基-苯基-吡唑啉部分的萘查耳酮。此处报告了这些化合物的完整 1H 和 13C NMR 数据，可用于进一步鉴定带有所需吡唑啉部分的新萘查耳酮。版权所有 © 2013 John Wiley & Sons, Ltd.
• 신규한 벤조칼콘 유도체 및 그 화합물을 포함하는 항암 조성물
  申请人：Konkuk University Industrial Cooperation Corp 건국대학교 산학협력단(220040157648) BRN ▼206-82-07325

  公开号：KR101540033B1

  公开（公告）日：2015-07-29

  본 발명은 신규한 벤조칼콘 유도체 및 그 화합물을 포함하는 항암 조성물에 관한 것이다.

  本发明涉及一种新型苯并咔唑衍生物及其包含的抗癌组合物。
• Synthetic Naphthoflavonoids Showing Inhibitory Effects on Clonogenicity against Cisplatin-Resistant A2780/Cis Human Ovarian Cancer Cells
  作者：Yearam Jung、Soon Young Shin、Yeonjoong Yong、Hyuk Yoon、Seunghyun Ahn、Hyeryoung Jung、Dongsoo Koh、Young Han Lee、Yoongho Lim

  DOI：10.2174/1570180812666150213230949

  日期：2015.7.30

  Detecting early-stage ovarian cancer, the fourth leading cause of cancerrelated deaths in women, is difficult, and the development of novel chemotherapeutic agents is required. Since several flavonoids show anticancer activities against ovarian cancer, 35 naphthylated flavonoids including 3’,4’-naphthochalcones, 5’,6’-naphthochalcone, 7,8-nap-hthoflavones, 5,6-naphthoflavanones, 5,6-naphthoflavones, 2,3-naphthochalcone, N-phenylpyrazolyl-5’,6’-naphthocha-lcones, carbothioamidepyrazolyl-5’,6’-naphthochalcones, pyrazolyl-3’,4’-naphthochalcone, and carbothioamidepyrazolyl-3’,4’-naphthochalcone were designed and synthesized. To explore the anticancer effects of these compounds, clonogenic long-term survival assays were applied on human cisplatin-resistant A2780/Cis ovarian cancer cells. Relationships between the structural properties of 35 naphthylated flavonoids and their clonogenicities were explored using comparative molecular field analysis and hologram quantitative structure– activity relationships. As a result, several structural features that increased cell growth inhibitory activity were identified, and a compound satisfying these conditions, 5-(2,3-dimethoxyphenyl)-3-(1-hydroxynaphthalen-2-yl)-N-phenyl-4,5-dihydro-1Hpyrazole- 1-carbothioamide, was designed and synthesized. This novel compound´s half-maximal cell growth inhibitory concentration was lower than those of the 35 flavonoid derivatives tested here. Therefore, the structural features observed in this report can be used to design and develop potent chemotherapeutic agents to treat ovarian cancer cells.

  早期卵巢癌的检测难度较大，而卵巢癌是女性癌症相关死亡的第四大原因，因此需要开发新型化疗药物。由于几种类黄酮显示出对卵巢癌的抗癌活性，本研究设计并合成了35种萘基类黄酮，包括3',4'-萘酮酮、5',6'-萘酮、7,8-萘黄酮、5,6-萘黄烷酮、5,6-萘黄酮、2,3-萘酮、N-苯基吡唑基-5',6'-萘酮、碳硫酰胺吡唑基-5',6'-萘酮、吡唑基-3',4'-萘酮及碳硫酰胺吡唑基-3',4'-萘酮。为了探索这些化합物的抗癌效果，采用了克隆形成长期存活实验，对人类顺铂耐药的A2780/Cis卵巢癌细胞进行实验。使用比较分子场分析和全息量化结构-活性关系探讨了35种萘基类黄酮的结构特性与它们的克隆形成能力之间的关系。结果表明，识别出几种可以增强细胞生长抑制活性的结构特征，进一步设计并合成了满足这些条件的化合物5-(2,3-二甲氧基苯基)-3-(1-羟基萘-2-基)-N-苯基-4,5-二氢-1H-吡唑-1-碳硫酰胺。该新型化合物的半最大细胞生长抑制浓度低于本文测试的35种类黄酮衍生物。因此，本报告中观察到的结构特征可用于设计和开发有效的化疗药物以治疗卵巢癌细胞。
• ¹ H and ¹³ C NMR spectral assignments of 18 novel polymethoxylated naphthochalcones bearing pyrazoline-1-carbothioamide groups
  作者：Hyeryoung Jung、Seunghyun Ahn、Mijoo Park、Hyuk Yoon、Hyung Jun Noh、Seung Yu Kim、Jin Sil Yoo、Dongsoo Koh、Yoongho Lim

  DOI：10.1002/mrc.4217

  日期：2015.5
• Anticancer and structure-activity relationship evaluation of 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide analogs of chalcone
  作者：Youngshim Lee、Beom Soo Kim、Seunghyun Ahn、Dongsoo Koh、Young Han Lee、Soon Young Shin、Yoongho Lim

  DOI：10.1016/j.bioorg.2016.08.003

  日期：2016.10

  To identify new potent chemotherapeutic agents, we synthesized compounds with 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide (NDPC) skeletons and evaluated their cytotoxicities using a clonogenic long-term survival assay. Their half-maximal cell growth inhibitory concentrations ranged from a few hundred nanomolars to a few micromolars. Further biological experiments including flow cytometry and western blotting analysis were performed with the derivative showing the best cytotoxicity. To identify a target protein of the selected compound, an in vitro kinase assay was carried out, which revealed that aurora kinases A and B were inhibited by the test compound, and this was confirmed using western blot analysis. The molecular binding mode between the selected compound and the kinases was elucidated using in silico docking. The structural conditions required for good cytotoxicity were identified based on the quantitative relationships between the physicochemical properties of the derivatives and their cytotoxicities. (C) 2016 Elsevier Inc. All rights reserved.