1-[5-(2,4-dimethoxyphenyl)-3-(4-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-l]ethanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[5-(2,4-dimethoxyphenyl)-3-(4-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-l]ethanone
• 英文别名: 1-[5-(2,4-Dimethoxy-phenyl)-3-(4-hydroxy-phenyl)-4,5-dihydro-pyrazol-1-yl]-ethanone；1-[3-(2,4-dimethoxyphenyl)-5-(4-hydroxyphenyl)-3,4-dihydropyrazol-2-yl]ethanone
• 化学式: C₁₉H₂₀N₂O₄
• 分子量: 340.379
• InChiKey: IAFZMTVQDVELPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[5-(2,4-dimethoxyphenyl)-3-(4-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-l]ethanone 在 对甲苯磺酰肼 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 30.0h， 以82.7%的产率得到4-(3-(2,4-dimethoxyphenyl)-1H-pyrazol-5-yl)phenol
  参考文献：
  名称：

  Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin

  摘要：

  Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with DHA against a panel of cancer cell lines. Unexpected sensitivity of 6f in Adriamycinresistant MCF-7 cells (MCF-7/Adr) inspired subsequent research on anticancer activity of these DHA derivatives against breast cancer cell lines. All the novel compounds exhibited potent activity in three breast cancer cells including MDA-MB-231, MCF-7 and MCF-7/Adr. Most of them exerted almost 10-fold higher potency in MCF-7/Adr than in MCF-7 and MDA-MB-231 cells. Compound 5f, the most potent compound against MCF-7/Adr (GI(50) = 18 nM), was used for mechanism research which revealed that compound 5f arrested MCF-7 and MCF-7/Adr cells in G0/G1 phase with decreased levels of cyclin D1 and increased levels of p27. Preliminary pharmacokinetic properties of 5f and 6f were investigated in rats after a single intravenous administration. The high sensitivity of MCF-7/Adr indicates that these compounds have potential to be developed as therapeutic agents to treat drug-resistant cancer. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.10.023
• 作为产物：
  描述：

  对羟基苯乙酮 在 一水合肼 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 10.0h， 生成 1-[5-(2,4-dimethoxyphenyl)-3-(4-hydroxyphenyl)-4,5-dihydro-1H-pyrazol-1-l]ethanone
  参考文献：
  名称：

  Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin

  摘要：

  Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with DHA against a panel of cancer cell lines. Unexpected sensitivity of 6f in Adriamycinresistant MCF-7 cells (MCF-7/Adr) inspired subsequent research on anticancer activity of these DHA derivatives against breast cancer cell lines. All the novel compounds exhibited potent activity in three breast cancer cells including MDA-MB-231, MCF-7 and MCF-7/Adr. Most of them exerted almost 10-fold higher potency in MCF-7/Adr than in MCF-7 and MDA-MB-231 cells. Compound 5f, the most potent compound against MCF-7/Adr (GI(50) = 18 nM), was used for mechanism research which revealed that compound 5f arrested MCF-7 and MCF-7/Adr cells in G0/G1 phase with decreased levels of cyclin D1 and increased levels of p27. Preliminary pharmacokinetic properties of 5f and 6f were investigated in rats after a single intravenous administration. The high sensitivity of MCF-7/Adr indicates that these compounds have potential to be developed as therapeutic agents to treat drug-resistant cancer. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.10.023

文献信息

• Design, synthesis and in vitro evaluation of some small molecules malonyl CoA decarboxylase inhibitors containing pyrazoline scaffold and study of their binding interactions with malonyl CoA decarboxylase via preliminary docking simulation
  作者：Deepali M. Jagdale、C. S. Ramaa

  DOI：10.1007/s00044-017-1917-7

  日期：2017.9

  In the present work series of small molecules (5a–5m, 6a–6j) were schematically designed and synthesized using simple chemical procedures. Their structures were confirmed based upon findings from infrared, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectra. The derivatives were evaluated for their in vitro malonyl CoA decarboxylase inhibition activity by using fluorimetric assay. Pyrazol-1-yl-1

  在本工作中，小分子（5a - 5m，6a - 6j）的序列是通过简单的化学程序进行示意图设计和合成的。基于红外，1H核磁共振（NMR），13C NMR和质谱的发现，确认了它们的结构。使用荧光测定法评估衍生物的体外丙二酰辅酶A脱羧酶抑制活性。吡唑-1-基-1、3-噻唑-4（5H）-一衍生物（5a - 5m）的活性优于吡唑-1-基-1-乙酮衍生物（6a - 6j）。化合物5e，5j，和6f表现出优异的体外丙二酰辅酶A脱羧酶抑制活性，IC50值分别为0.10、0.27和0.26μM。将这些活性最高的化合物5e，5j和6f停靠在丙二酰辅酶A脱羧酶（HsMCD，PDB ID：2YGW）中，以研究配体与蛋白质的相互作用。
• Synthesis and Selective Inhibitory Activity of 1-Acetyl-3,5-diphenyl-4,5-dihydro-(1<i>H</i>)-pyrazole Derivatives against Monoamine Oxidase
  作者：Franco Chimenti、Adriana Bolasco、Fedele Manna、Daniela Secci、Paola Chimenti、Olivia Befani、Paola Turini、Valentina Giovannini、Bruno Mondovì、Roberto Cirilli、Francesco La Torre

  DOI：10.1021/jm031042b

  日期：2004.4.1

  A novel series of 1-acetyl-3-(4-hydroxy- and 2,4-dihydroxyphenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole derivatives 1 - 12 have been synthesized and investigated for the ability to selectively inhibit the activity of the A and B isoforms of monoamine oxidase (MAO). The new synthesized compounds 1-12 proved to be more reversible, potent, and selective inhibitors of MAO-A than of MAO-B. Knowing that stereochemistry may be an important modulator of biological activity, we performed the semipreparative chromatographic enantioseparation of the most potent, selective, and chiral compounds, 6 and 11. The separated enantiomers were then submitted to in vitro biological evaluation while increasing their inhibitory activity and A selectivity. The (-)-6 enantiomer shows Ki(MAO-A) 2 nM and SI = 165 000, (+)-6 shows Ki(MAO-A) = 6 nM and SI = 166 666, (-)-11 shows Ki(MAO-A) = 4 nM and SI = 80 000, and (+)-11 shows Ki(MAO-A) = 7 nM and SI = 38 571.