1-(3,4-二甲基苯基)-1H,4H-吡唑啉-3,5-二酮 | 277299-73-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(3,4-二甲基苯基)-1H,4H-吡唑啉-3,5-二酮
• 英文名称: 1-(3,4-dimethylphenyl)-1H,4H-pyrazoline-3,5-dione
• 英文别名: WECC-0055263；1-(3,4-Dimethylphenyl)-1H,4H-pyrazolin-3,5-dione；1-(3,4-dimethylphenyl)pyrazolidine-3,5-dione
• CAS: 277299-73-7
• 化学式: C₁₁H₁₂N₂O₂
• mdl: MFCD00821768
• 分子量: 204.228
• InChiKey: XWLIFZHBTPRPDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3,4-二甲基苯基)-1H,4H-吡唑啉-3,5-二酮 在 3 A molecular sieve 、 硫酸 、 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Hydrazinonaphthalene and Azonaphthalene Thrombopoietin Mimics Are Nonpeptidyl Promoters of Megakaryocytopoiesis

  摘要：

  High-throughput screening for the induction of a luciferase reporter gene in a thrombopoietin (TPO)-responsive cell line resulted in the identification of 4-diazo-3-hydroxy-1-naphthalene-sulfonic acids as TPO mimics. Modification of the core structure and adjustment of unwanted functionality resulted in the development of (5-oxo-1,5-dihydropyrazol-4-ylidene)hydrazines which exhibited efficacies equivalent to those of TPO in several cell-based assays designed to measure thrombopoietic activity. Furthermore, these compounds elicited biochemical responses in TPO-receptor-expressing cells similar to those in TPO itself, including kinase activation and protein phosphorylation. Potencies for the best compounds were high for such low molecular weight compounds (MW < 500) with EC50 values in the region of 1-20 nM.

  DOI：

  10.1021/jm010283l
• 作为产物：
  描述：

  3,4-二甲基苯肼 在 三氯氧磷 作用下， 以 乙醚 为溶剂， 反应 0.17h， 生成 1-(3,4-二甲基苯基)-1H,4H-吡唑啉-3,5-二酮
  参考文献：
  名称：

  Hydrazinonaphthalene and Azonaphthalene Thrombopoietin Mimics Are Nonpeptidyl Promoters of Megakaryocytopoiesis

  摘要：

  High-throughput screening for the induction of a luciferase reporter gene in a thrombopoietin (TPO)-responsive cell line resulted in the identification of 4-diazo-3-hydroxy-1-naphthalene-sulfonic acids as TPO mimics. Modification of the core structure and adjustment of unwanted functionality resulted in the development of (5-oxo-1,5-dihydropyrazol-4-ylidene)hydrazines which exhibited efficacies equivalent to those of TPO in several cell-based assays designed to measure thrombopoietic activity. Furthermore, these compounds elicited biochemical responses in TPO-receptor-expressing cells similar to those in TPO itself, including kinase activation and protein phosphorylation. Potencies for the best compounds were high for such low molecular weight compounds (MW < 500) with EC50 values in the region of 1-20 nM.

  DOI：

  10.1021/jm010283l

文献信息

• Thrombopoietin mimetics
  申请人：——

  公开号：US20040019190A1

  公开（公告）日：2004-01-29

  Invented are non-peptide TPO mimetics. Also invented are novel processes and intermediates used in the preparation of the presently invented compounds. Also invented is a method of treating thrombocytopenia, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a selected hydroxy- 1 -azobenzene derivative.

  发明了非肽类TPO类似物。还发明了用于制备目前发明的化合物的新工艺和中间体。还发明了一种治疗血小板减少症的方法，包括给予需要的哺乳动物，包括人类，有效量的选择性羟基-1-偶氮苯衍生物。
• Discovering potent inhibitors against c-Met kinase: molecular design, organic synthesis and bioassay
  作者：Zhongjie Liang、Xiao Ding、Jing Ai、Xiangqian Kong、Limin Chen、Liang Chen、Cheng Luo、Meiyu Geng、Hong Liu、Kaixian Chen、Hualiang Jiang

  DOI：10.1039/c1ob06186k

  日期：——

  A substructure similarity search against the SPECS database and chemical synthesis methods were performed to obtain a series of pyrazolidine-3,5-dione derivatives. Through the enzyme-based assay against c-Met kinase, 4 compounds (1c, 1e, 1m and 1o) showed potential inhibitory activity, with IC50 values mostly less than 10 μM. Based on the structure–activity relationship (SAR) and binding mode analysis

  受体酪氨酸激酶c-Met是当今治疗癌症的诱人靶标。小分子抑制剂的发现在c-Met激酶途径的阻断中特别有意义。在这里，我们从化合物1a开始研究，化合物1a是一种新型的c-Met激酶抑制剂。针对SPECS数据库的子结构相似性搜索和化学合成方法，获得了一系列吡唑烷-3,5-二酮衍生物。通过针对c-Met激酶的基于酶的测定，四种化合物（1c，1e，1m和1o）显示出潜在的抑制活性，IC 50值通常小于10μM。基于结构-活性关系（SAR）和结合模式分析，LD1.0程序设计了一个有针对性的组合库。考虑到ADMET的性质和可合成性，成功合成了七个候选化合物（5a–g）。最有效的化合物5b（IC 50 = 0.46μM）的活性是铅1a的20倍。综上所述，我们的发现确定吡唑烷-3,5-二酮衍生物是抗c-Met激酶的有效抑制剂，并证明了该策略在开发抗c-Met激酶的小分子中的有效性。
• THROMBOPOIETIN MIMETICS
  申请人：Duffy Kevin J.

  公开号：US20130078213A1

  公开（公告）日：2013-03-28

  Invented are non-peptide TPO mimetics. Also invented are novel processes and intermediates used in the preparation of the presently invented compounds. Also invented is a method of treating thrombocytopenia, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a selected hydroxy-1-azobenzene derivative.

  本发明涉及非肽类TPO类似物的发明。本发明还涉及用于制备目前发明的化合物的新型过程和中间体。本发明还涉及一种治疗血小板减少症的方法，包括在需要的哺乳动物（包括人类）中给予所选的羟基-1-偶氮苯衍生物的有效量。
• EP1294378A4
  申请人：——

  公开号：EP1294378A4

  公开（公告）日：2004-01-28
• US6670387B1
  申请人：——

  公开号：US6670387B1

  公开（公告）日：2003-12-30