5-tert-butyl-2-(3,4-dimethylphenyl)-2,4-dihydropyrazol-3-onene | 374924-86-4

• 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: 5-tert-butyl-2-(3,4-dimethylphenyl)-2,4-dihydropyrazol-3-onene
• 英文别名: 5-tert-butyl-2-(3,4-dimethylphenyl)-2,4-dihydropyrazol-3-one；3-tert-Butyl-1-(3,4-dimethylphenyl)-3-pyrazolin-5-one；5-tert-butyl-2-(3,4-dimethylphenyl)-4H-pyrazol-3-one
• CAS: 374924-86-4
• 化学式: C₁₅H₂₀N₂O
• 分子量: 244.337
• InChiKey: JZXOXTMOVGCULA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-tert-butyl-2-(3,4-dimethylphenyl)-2,4-dihydropyrazol-3-onene 、 1,2-萘氧基-二氮杂唑-4-磺酸 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 以88%的产率得到
  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：

  特戊酰基乙酸乙酯 、 3,4-二甲基苯肼 在 溶剂黄146 作用下， 反应 24.0h， 以55%的产率得到5-tert-butyl-2-(3,4-dimethylphenyl)-2,4-dihydropyrazol-3-onene
  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。
• 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
• [EN] THROMBOPOIETIN MIMETICS<br/>[FR] MIMIQUES DE THROMBOPOIETINE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2001089457A2

  公开（公告）日：2001-11-29

  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.
• Hydrazinonaphthalene and Azonaphthalene Thrombopoietin Mimics Are Nonpeptidyl Promoters of Megakaryocytopoiesis
  作者：Kevin J. Duffy、Michael G. Darcy、Evelyne Delorme、Susan B. Dillon、Daniel F. Eppley、Connie Erickson-Miller、Leslie Giampa、Christopher B. Hopson、Yifang Huang、Richard M. Keenan、Peter Lamb、Lynnette Leong、Nannan Liu、Stephen G. Miller、Alan T. Price、Jon Rosen、Rakhi Shah、Tony N. Shaw、Heather Smith、Kenneth C. Stark、Shin-Shay Tian、Curtis Tyree、Kenneth J. Wiggall、Lily Zhang、Juan I. Luengo

  DOI：10.1021/jm010283l

  日期：2001.10.1

  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.