4-(1H-indol-3-ylmethylene)-5-methyl-2-phenyl-2,4-dihydropyrazol-3-one | 43106-26-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-(1H-indol-3-ylmethylene)-5-methyl-2-phenyl-2,4-dihydropyrazol-3-one
• 英文别名: 4-((1H-indol-3-yl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one；4-(3-indolylmethylene)-3-methyl-1-phenylpyrazolin-5-one；4-indol-3-ylmethylene-5-methyl-2-phenyl-2,4-dihydro-pyrazol-3-one
• CAS: 43106-26-9
• 化学式: C₁₉H₁₅N₃O
• 分子量: 301.348
• InChiKey: JLTZOAZBWCMUCX-UHFFFAOYSA-N

物化性质

• 熔点：
  228-230 °C
• 沸点：
  513.6±60.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  48.46
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-(1H-indol-3-ylmethylene)-5-methyl-2-phenyl-2,4-dihydropyrazol-3-one 在 aluminum (III) chloride 、 sodium hydride 作用下， 以 二氯甲烷 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 13.5h， 生成 4-((1-(2-hydroxy-3-(3-morpholinopropylamino)propyl)-1H-indol-3-yl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one
  参考文献：
  名称：

  The discovery of indole derivatives as novel hepatitis C virus inhibitors

  摘要：

  In this study, a library of in-house small molecule was screened using a HCV cell-based assay and a compound (1) containing an N-protected indole scaffold (NINS) was identified as a novel anti-HCV inhibitor. Through structure activity relationship (SAR) study, it was observed that the racemic inhibitor (10m) displayed good anti-HCV activity (EC50 = 1.02 +/- 0.10 mu M) with the excellent selectivity index (SI = 45.56). Interestingly, R-enantiomer ((R)-10m) showed better anti-HCV activity and lower cytotoxicity than S-enantiomer ((S)-10m). (R)-10m gave the best anti-HCV potency (EC50 = 0.72 +/- 0.09 mu M) with the highest selectivity index (SI > 69.44). In addition, the mechanism of action study of NINS derivatives demonstrated that NINS derivatives interfere with the early step (viral entry) of the HCV life cycle. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.062
• 作为产物：
  描述：

  依达拉奉 在 溶剂黄146 作用下， 以 乙醇 、 二甲胺 为溶剂， 反应 2.25h， 生成 4-(1H-indol-3-ylmethylene)-5-methyl-2-phenyl-2,4-dihydropyrazol-3-one
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of indolylidinepyrazolones as potential anti-bacterial agents

  摘要：

  DOI：

  10.1016/j.tetlet.2014.05.131

文献信息

• Synthesis and Molluscicidal Activity of New Chromene and Pyrano[2,3-c]pyrazole Derivatives
  作者：Fathy M. Abdelrazek、Peter Metz、Olga Kataeva、Anne Jäger、Sherif F. El-Mahrouky

  DOI：10.1002/ardp.200700157

  日期：2007.10

  derivatives 13a–d to afford the arylidene exchange derivatives 14a–c and the pyranopyrazole derivative 15, respectively. The arylidene derivatives 10a, b react also with indane‐1,3‐dione 16 to afford the arylidene exchange derivatives 18a, b. The molluscicidal activity of the synthesized compounds towards Biomphalaria alexandrina snails, the intermediate host of Schistosoma mansoni, was investigated and most

  色烯衍生物4与乙酸酐、异硫氰酸苯酯和原甲酸乙酯反应，分别得到N-乙酰衍生物6、色烯嘧啶8和甲酰亚胺酯9。2- (1H - Indol - 3-ylmethylene)-丙二腈 10b 与 1,3- 环己二酮和二甲酮 11a、b 反应，分别得到 4（3-吲哚基）-色烯衍生物 12a、b，并与吡唑啉酮衍生物 13a- d 分别得到亚芳基交换衍生物 14a-c 和吡喃并吡唑衍生物 15。亚芳基衍生物10a、b也与茚满-1,3-二酮16反应得到亚芳基交换衍生物18a、b。研究了合成的化合物对曼氏血吸虫的中间宿主 Biomphalaria alexandrina 蜗牛的杀软体动物活性，其中大多数表现出弱到中等的活性。
• Discovery of novel inhibitors of human phosphoglycerate dehydrogenase by activity-directed combinatorial chemical synthesis strategy
  作者：Xia Zhou、Yuping Tan、Kun Gou、Lei Tao、Yuan Luo、Yue Zhou、Zeping Zuo、Qingxiang Sun、Youfu Luo、Yinglan Zhao

  DOI：10.1016/j.bioorg.2021.105159

  日期：2021.10

  adopted activity-directed combinatorial chemical synthesis strategy to optimize this hit compound. Compound b36 was found to be the noncompetitive and the most promising one with IC50 values of 5.96 ± 0.61 μM against PHGDH. Compound b36 inhibited the proliferation of human breast cancer and ovarian cancer cells, reduced intracellular serine synthesis, damaged DNA synthesis, and induced cell cycle arrest

  丝氨酸是从头合成嘌呤和脱氧胸苷所必需的一碳单元的来源，在癌细胞的生长中起着至关重要的作用。磷酸甘油酸脱氢酶 (PHGDH) 催化丝氨酸从头生物合成中的第一个限速步骤，已成为治疗癌症的有希望的靶点。在这里，我们从基于酶促测定的内部小分子库的筛选中确定了H-G6作为潜在的 PHGDH 抑制剂。我们采用了活性导向的组合化学合成策略来优化这种命中化合物。发现化合物b36是非竞争性和最有前途的化合物，其对 PHGDH 的IC 50值为 5.96 ± 0.61 μM。化合物b36抑制人乳腺癌和卵巢癌细胞的增殖，减少细胞内丝氨酸合成，破坏DNA合成，并诱导细胞周期停滞。总的来说，我们的结果表明b36是一种新型的 PHGDH 抑制剂，它可能是一种有前景的调节丝氨酸合成途径的调节剂，并且可能是一种潜在的抗癌先导物，值得进一步探索。
• Moriya, Tamon; Hagio, Katsuaki; Yoneda, Naoto, Chemical and pharmaceutical bulletin, 1980, vol. 28, # 6, p. 1711 - 1721
  作者：Moriya, Tamon、Hagio, Katsuaki、Yoneda, Naoto

  DOI：——

  日期：——