3-(3-chloro-4-hydroxyphenyl)-N-(2-(piperidin-1-yl)ethyl)-4-(pyridin-4-yl)-1H-pyrazole-1-carboxamide | 1309606-13-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(3-chloro-4-hydroxyphenyl)-N-(2-(piperidin-1-yl)ethyl)-4-(pyridin-4-yl)-1H-pyrazole-1-carboxamide
• 英文别名: 3-(3-chloro-4-hydroxyphenyl)-N-(2-piperidin-1-ylethyl)-4-pyridin-4-ylpyrazole-1-carboxamide
• CAS: 1309606-13-0
• 化学式: C₂₂H₂₄ClN₅O₂
• 分子量: 425.918
• InChiKey: OFNCRASYGZCTFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  83.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,4-二氯苯甲酸 在 三氟二甲基硫醚络合物 、 三乙胺 、 乙酰氯 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 六甲基磷酰三胺 、 二氯甲烷 为溶剂， 反应 84.0h， 生成 3-(3-chloro-4-hydroxyphenyl)-N-(2-(piperidin-1-yl)ethyl)-4-(pyridin-4-yl)-1H-pyrazole-1-carboxamide
  参考文献：
  名称：

  Design and Synthesis of 3-(3-Chloro-4-substituted phenyl)-4-(pyridin-4-yl)-1Hpyrazole- 1-carboxamide Derivatives and Their Antiproliferative Activity Against Melanoma Cell Line

  摘要：

  描述了新型3,4-二芳基吡唑-1-氨基甲酸酯衍生物的设计和合成。测试了它们对A375人黑色素瘤细胞系的抗增殖活性，并研究了取代基对二芳基吡唑骨架的影响。药理结果表明，与索拉非尼相比，大多数合成的化合物对A375显示出中等活性。另一方面，化合物Ia、Ie、IIb和IIh的活性优于索拉非尼。此外，化合物IIa的活性与索拉非尼相当。在所有这些衍生物中，化合物IIb含有二乙基氨基和酚类基团，显示出对A375人黑色素瘤细胞系最强的抗增殖活性。通过将活性最强的化合物IIb对接至V600E-b-Raf的结构域，进行了虚拟筛选，并研究了其结合模式。

  DOI：

  10.5012/bkcs.2011.32.3.821

文献信息

• Antiproliferative Diarylpyrazole Derivatives as Dual Inhibitors of the ERK Pathway and COX-2
  作者：Mohammed I. El-Gamal、Hong Seok Choi、Kyung Ho Yoo、Daejin Baek、Chang-Hyun Oh

  DOI：10.1111/cbdd.12186

  日期：2013.9

  A series of 3,4‐diarylpyrazole‐1‐carboxamide derivatives was designed and synthesized. A selected group of the target compounds was tested for in vitro antiproliferative activities over a panel of 60 cancer cell lines at the National Cancer Institute (NCI, Bethesda, MD, USA) at a single‐dose concentration of 10 μm, and the four most active compounds 9a, 9l, 9n, and 10o were further tested in a five‐dose testing mode to determine their IC50 values over the 60 cell lines. In addition, a selected group of target compounds were tested for inhibitory effect over cyclooxygenase isozymes. Compounds 9a, 9l, 9n, and 10o were also tested for MEK and ERK kinase inhibitory activity using Western blot assay. Compound 10o was selective toward melanoma cell line subpanel, and its antiproliferative activity may be attributed to selective cyclooxygenase‐2 inhibition and ERK pathway inhibition.
• Design and Synthesis of 3-(3-Chloro-4-substituted phenyl)-4-(pyridin-4-yl)-1Hpyrazole- 1-carboxamide Derivatives and Their Antiproliferative Activity Against Melanoma Cell Line
  作者：Mohammed I. El-Gamal、Chang-Hyun Oh

  DOI：10.5012/bkcs.2011.32.3.821

  日期：2011.3.20

  Design and synthesis of new 3,4-diarylpyrazole-1-carboxamide derivatives are described. Their antiproliferative activity against A375 human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The pharmacological results indicated that most of the synthesized compounds showed moderate activity against A375, compared with Sorafenib. On the other hand, compounds Ia, Ie, IIb, and IIh were more potent than Sorafenib. In addition, compound IIa was equipotent to Sorafenib. Among all of these derivatives, compound IIb which has diethylamino and phenolic moieties showed the most potent antiproliferative activity against A375 human melanoma cell line. Virtual screening was carried out through docking of the most potent compound IIb into the domain of V600E-b-Raf and the binding mode was studied.

  描述了新型3,4-二芳基吡唑-1-氨基甲酸酯衍生物的设计和合成。测试了它们对A375人黑色素瘤细胞系的抗增殖活性，并研究了取代基对二芳基吡唑骨架的影响。药理结果表明，与索拉非尼相比，大多数合成的化合物对A375显示出中等活性。另一方面，化合物Ia、Ie、IIb和IIh的活性优于索拉非尼。此外，化合物IIa的活性与索拉非尼相当。在所有这些衍生物中，化合物IIb含有二乙基氨基和酚类基团，显示出对A375人黑色素瘤细胞系最强的抗增殖活性。通过将活性最强的化合物IIb对接至V600E-b-Raf的结构域，进行了虚拟筛选，并研究了其结合模式。