methyl 3-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate | 881473-42-3

• 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: methyl 3-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate
• 英文别名: methyl 3-(3-methyl-5-oxo-4H-pyrazol-1-yl)benzoate
• CAS: 881473-42-3
• 化学式: C₁₂H₁₂N₂O₃
• 分子量: 232.239
• InChiKey: XRULIERBJACBQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate 、 5-(4,5-二甲基-2-硝基-苯基)-呋喃-2-甲醛 在 二乙胺 作用下， 以 乙醇 为溶剂， 生成 methyl 3-[4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoate
  参考文献：
  名称：

  Virtual Ligand Screening of the p300/CBP Histone Acetyltransferase: Identification of a Selective Small Molecule Inhibitor

  摘要：

  The histone acetyltransferase (HAT) p300/CBP is a transcriptional coactivator implicated in many gene regulatory pathways and protein acetylation events. Although p300 inhibitors have been reported, a potent, selective, and readily available active-site-directed small molecule inhibitor is not yet known. Here we use a structure-based, in silico screening approach to identify a commercially available pyrazolone-containing small molecule p300 HAT inhibitor, C646. C646 is a competitive p300 inhibitor with a K-i of 400 nM and is selective versus other acetyltransferases. Studies on site-directed p300 HAT mutants and synthetic modifications of C646 confirm the importance of predicted interactions in conferring potency. Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target.

  DOI：

  10.1016/j.chembiol.2010.03.006
• 作为产物：
  描述：

  3-氨基苯甲酸甲酯 在 盐酸 、 溶剂黄146 、 sodium nitrite 作用下， 反应 12.0h， 生成 methyl 3-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate
  参考文献：
  名称：

  Virtual Ligand Screening of the p300/CBP Histone Acetyltransferase: Identification of a Selective Small Molecule Inhibitor

  摘要：

  The histone acetyltransferase (HAT) p300/CBP is a transcriptional coactivator implicated in many gene regulatory pathways and protein acetylation events. Although p300 inhibitors have been reported, a potent, selective, and readily available active-site-directed small molecule inhibitor is not yet known. Here we use a structure-based, in silico screening approach to identify a commercially available pyrazolone-containing small molecule p300 HAT inhibitor, C646. C646 is a competitive p300 inhibitor with a K-i of 400 nM and is selective versus other acetyltransferases. Studies on site-directed p300 HAT mutants and synthetic modifications of C646 confirm the importance of predicted interactions in conferring potency. Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target.

  DOI：

  10.1016/j.chembiol.2010.03.006

文献信息

• USE OF HISTONE ACETYLTRANSFERASE INHIBITORS AS NOVEL ANTI-CANCER THERAPIES
  申请人：Alani Rhoda Myra

  公开号：US20130142887A1

  公开（公告）日：2013-06-06

  The present invention provides methods for treating cancer comprising inhibiting the activity of p300/CBP histone acetyltransferase (HAT). Also provided are p300/CBP HAT inhibitors for treating a subject having cancer. In addition, the present invention includes biomarkers for p300/CBP HAT inhibition, which are used to i) monitor the effectiveness of cancer therapy, and ii) identify anti-cancer agents for use in combination therapy.

  本发明提供了用于治疗癌症的方法，包括抑制p300/CBP组蛋白乙酰转移酶（HAT）的活性。同时，本发明还提供了用于治疗患有癌症的受试者的p300/CBP HAT抑制剂。此外，本发明包括用于p300/CBP HAT抑制的生物标志物，用于i）监测癌症治疗的有效性，和ii）识别用于联合治疗的抗癌剂。
• Discovery of new Gram-negative antivirulence drugs: Structure and properties of novel E. coli WaaC inhibitors
  作者：F. Moreau、N. Desroy、J.M. Genevard、V. Vongsouthi、V. Gerusz、G. Le Fralliec、C. Oliveira、S. Floquet、A. Denis、S. Escaich、K. Wolf、M. Busemann、A. Aschenbrenner

  DOI：10.1016/j.bmcl.2008.05.117

  日期：2008.7

  Heptosyltransferases such as WaaC represent promising and attractive targets for the discovery of new Gram-negative antibacterial drugs based on antivirulence mechanisms. We report herein our approach to the identification of the first micromolar inhibitors of WaaC and the preliminary SAR generated from this family of 2-aryl-5-methyl-4-(5-aryl-furan-2-yl-methylene)-2,4-dihydro-pyrazol-3-ones identified by virtual screening. (c) 2008 Elsevier Ltd. All rights reserved.
• US9005670B2
  申请人：——

  公开号：US9005670B2

  公开（公告）日：2015-04-14
• [EN] USE OF HISTONE ACETYLTRANSFERASE INHIBITORS AS NOVEL ANTI-CANCER THERAPIES<br/>[FR] UTILISATION D'INHIBITEURS DE L'HISTONE ACÉTYLTRANSFÉRASE EN TANT QUE NOUVELLES THÉRAPIES ANTICANCÉREUSES
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2011085039A2

  公开（公告）日：2011-07-14

  The present invention provides methods for treating cancer comprising inhibiting the activity of p300/CBP histone acetyltransferase (HAT). Also provided are p300/CBP HAT inhibitors for treating a subject having cancer. In addition, the present invention includes biomarkers for p300/CBP HAT inhibition, which are used to i) monitor the effectiveness of cancer therapy, and ii) identify anti-cancer agents for use in combination therapy.