1,5-diphenyl-3-methyl-4-formylpyrazole | 41461-99-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,5-diphenyl-3-methyl-4-formylpyrazole
• 英文别名: 3-methyl-1,5-diphenyl-1H-pyrazole-4-carbaldehyde；4-Formyl-3-methyl-1.5-diphenyl-pyrazol；4-Formyl-1,5-diphenyl-3-methyl-pyrazol；3-Methyl-1,5-diphenyl-1H-pyrazol-4-carbaldehyd；3-methyl-1,5-diphenylpyrazole-4-carbaldehyde
• CAS: 41461-99-8
• 化学式: C₁₇H₁₄N₂O
• 分子量: 262.311
• InChiKey: UZDZTHBITZFWCX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,5-diphenyl-3-methyl-4-formylpyrazole 在 jones reagent 作用下， 以 丙酮 为溶剂， 反应 0.5h， 以96%的产率得到3-methyl-1,5-diphenylpyrazole-4-carboxylic acid
  参考文献：
  名称：

  Novel 1,5-Diphenylpyrazole Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors with Enhanced Activity versus the Delavirdine-Resistant P236L Mutant:  Lead Identification and SAR of 3- and 4-Substituted Derivatives

  摘要：

  Through computationally directed broad screening, a novel 1,5-diphenylpyrazole (DPP) class of HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been discovered. Compound 2 (PNU-32945) was found to have good activity versus wild-type (IC50 = 2.3 mu M) and delavirdine-resistant P236L (IC50 = 1.1 mu M) reverse transcriptase IRT). Also, PNU-32945 has an ED50 for inhibition of viral replication in cell cultures of 0.1 mu M and was shown to be noncytotoxic with a CC50 > 10 mu M. Structure-activity relationship studies on the 3- and 4-positions of PNU-32945 led to interesting selectivity and activity within the class. In particular, the 3-hydroxyethyl-4-ethyl congener 29 is a potent inhibitor of the P236L mutant (IC50 = 0.65 mu M), whereas it is essentially inactive versus the wild-type enzyme (IC50 > 50 mu M). Furthermore, this compound was significantly more active versus the P236L mutant than delavirdine. The synthesis and RT inhibitory activity of various 3- and 4-substituted analogues are discussed.

  DOI：

  10.1021/jm990383f
• 作为产物：
  描述：

  苯肼 在 potassium carbonate 、 溶剂黄146 、 三氯氧磷 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 1,5-diphenyl-3-methyl-4-formylpyrazole
  参考文献：
  名称：

  作为鞘氨醇激酶-1 抑制剂的新型吡唑基苯并咪唑的设计与合成

  摘要：

  鞘氨醇 1 激酶 (SphK1) 是磷脂的重要酶之一，其抑制是不同疾病的治疗策略之一。在不同类型的癌症中观察到 SphK1 过表达，表明其在肿瘤生长中的重要作用。为了寻找有效的 SphK1 抑制剂，合成了一系列新的吡唑基苯并咪唑并作为鞘氨醇激酶-1 (SphK1) 抑制剂进行了评估。为了评估所有合成化合物的结合亲和力，对所有化合物进行对接分析和荧光猝灭。结果表明，对接和荧光猝灭结果具有一致性，表明化合物47和48SphK1 的荧光强度显着降低，并形成稳定的蛋白质-配体复合物。此外，还进行了酶抑制试验，显示出对 SphK1 的有效抑制潜力。此外，IC 50值显示化合物47和48是最有希望的化合物。此外，针对 NCI-60 细胞系面板对所有合成化合物进行了抗增殖研究。目标化合物47和48证明了对癌细胞系的有效抗肿瘤活性和生长抑制潜力。大多数这些化合物都非常适合 SphK1 的 ATP 结合位点

  DOI：

  10.1007/s00044-021-02760-3

文献信息

• Molecular modeling and synthesis of new 1,5-diphenylpyrazoles as breast cancer cell growth inhibitors
  作者：Wafaa A. Ewes、Sahar M.I. Badr、Hassan M. Eisa、Magda N.A. Nasr

  DOI：10.1515/hc-2015-0156

  日期：2015.12.1

  Abstract New pyrazoles have been synthesized and evaluated as breast cancer cell growth inhibitors. Condensation of the substituted pyrazole-4-carbaldehyde 1 with acetophenone and chloroacetophenone afforded α, β-unsaturated ketones 2 and 3, respectively. Compounds 2 and 3 were subjected to different reactions using hydrazine hydrate, substituted hydrazine hydrate, hydroxylamine, o-phenylenediamine

  摘要 新的吡唑类化合物已被合成并评估为乳腺癌细胞生长抑制剂。取代的吡唑-4-甲醛 1 与苯乙酮和氯苯乙酮缩合，分别得到 α、β-不饱和酮 2 和 3。使用水合肼、取代水合肼、羟胺、邻苯二胺、丙二腈在不同条件下对化合物 2 和 3 进行不同反应，得到 4-取代的吡唑衍生物 4-28。使用IR、1H NMR、13C NMR、质谱数据和元素分析对这些化合物进行结构解析。针对 MCF-7 细胞系（人乳腺癌）测试了目标化合物的抗肿瘤活性。化合物4、10和20对乳腺癌具有显着的抗肿瘤活性。
• Synthesis of dibenzopyranones and pyrazolobenzopyranones through copper(0)/Selectfluor system-catalyzed double CH activation/oxygen insertion of 2-arylbenzaldehydes and 5-arylpyrazole-4-carbaldehydes
  作者：Jian Zhang、Dongdong Shi、Haifeng Zhang、Zheng Xu、Hanyang Bao、Hongwei Jin、Yunkui Liu

  DOI：10.1016/j.tet.2016.11.069

  日期：2017.1

  A mild and efficient protocol for the synthesis of dibenzopyranones and pyrazolobenzopyranones was developed involving a copper(0)/Selectfluor system-catalyzed double C-H activation/oxygen insertion of 2-arylbenzaldehydes and 5-arylpyrazole-4-carbaldehydes. Preliminary mechanistic studies suggest that both water and dioxygen act as the oxygen source in the formation of pyranone scaffolds. (C) 2016 Elsevier Ltd. All rights reserved.
• Novel 1,5-Diphenylpyrazole Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors with Enhanced Activity versus the Delavirdine-Resistant P236L Mutant:  Lead Identification and SAR of 3- and 4-Substituted Derivatives
  作者：Michael J. Genin、Carolyn Biles、Barb J. Keiser、Susan M. Poppe、Steven M. Swaney、W. Gary Tarpley、Yoshihiko Yagi、Donna L. Romero

  DOI：10.1021/jm990383f

  日期：2000.3.1

  Through computationally directed broad screening, a novel 1,5-diphenylpyrazole (DPP) class of HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been discovered. Compound 2 (PNU-32945) was found to have good activity versus wild-type (IC50 = 2.3 mu M) and delavirdine-resistant P236L (IC50 = 1.1 mu M) reverse transcriptase IRT). Also, PNU-32945 has an ED50 for inhibition of viral replication in cell cultures of 0.1 mu M and was shown to be noncytotoxic with a CC50 > 10 mu M. Structure-activity relationship studies on the 3- and 4-positions of PNU-32945 led to interesting selectivity and activity within the class. In particular, the 3-hydroxyethyl-4-ethyl congener 29 is a potent inhibitor of the P236L mutant (IC50 = 0.65 mu M), whereas it is essentially inactive versus the wild-type enzyme (IC50 > 50 mu M). Furthermore, this compound was significantly more active versus the P236L mutant than delavirdine. The synthesis and RT inhibitory activity of various 3- and 4-substituted analogues are discussed.
• Design and synthesis of new pyrazolylbenzimidazoles as sphingosine kinase-1 inhibitors
  作者：Shadia A. Galal、Mohamed A. Omar、Sarah H. M. Khairat、Fatma A. F. Ragab、Sonam Roy、Ahmad Abu Turab Naqvi、Md. Imtaiyaz Hassan、Hoda I. El Diwani

  DOI：10.1007/s00044-021-02760-3

  日期：2021.9

  observed in different types of cancer indicating its important role in tumor growth. In search of effective SphK1 inhibitors, a new series of pyrazolylbenzimidazoles was synthesized and evaluated as sphingosine kinase-1 (SphK1) inhibitors. In order to evaluate the binding affinities of all the synthesized compounds, all compounds were subjected to docking analysis and fluorescence quenching. The results

  鞘氨醇 1 激酶 (SphK1) 是磷脂的重要酶之一，其抑制是不同疾病的治疗策略之一。在不同类型的癌症中观察到 SphK1 过表达，表明其在肿瘤生长中的重要作用。为了寻找有效的 SphK1 抑制剂，合成了一系列新的吡唑基苯并咪唑并作为鞘氨醇激酶-1 (SphK1) 抑制剂进行了评估。为了评估所有合成化合物的结合亲和力，对所有化合物进行对接分析和荧光猝灭。结果表明，对接和荧光猝灭结果具有一致性，表明化合物47和48SphK1 的荧光强度显着降低，并形成稳定的蛋白质-配体复合物。此外，还进行了酶抑制试验，显示出对 SphK1 的有效抑制潜力。此外，IC 50值显示化合物47和48是最有希望的化合物。此外，针对 NCI-60 细胞系面板对所有合成化合物进行了抗增殖研究。目标化合物47和48证明了对癌细胞系的有效抗肿瘤活性和生长抑制潜力。大多数这些化合物都非常适合 SphK1 的 ATP 结合位点