1-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)-3-(4-chlorophenyl)urea | 1160934-69-9

• 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-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)-3-(4-chlorophenyl)urea
• 英文别名: Pyrazolourea, 1a；1-[2-(3-aminophenyl)-5-tert-butylpyrazol-3-yl]-3-(4-chlorophenyl)urea
• CAS: 1160934-69-9
• 化学式: C₂₀H₂₂ClN₅O
• 分子量: 383.881
• InChiKey: OOEIYCDNOQOFJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  85
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(3-tert-butyl-1-(3-nitrophenyl)-1H-pyrazol-5-yl)-3-(4-chlorophenyl)urea 在 镍 、 氯化铵 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以62%的产率得到1-(1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl)-3-(4-chlorophenyl)urea
  参考文献：
  名称：

  Hybrid Compound Design To Overcome the Gatekeeper T338M Mutation in cSrc

  摘要：

  The emergence of drug resistance remains a fundamental challenge in the development of kinase inhibitors that are effective over long-term treatments. Allosteric inhibitors that bind to sites lying outside the highly conserved ATP pocket are thought to be more selective than ATP-competitive inhibitors and may circumvent some mechanisms of drug resistance. Crystal structures of type I and allosteric type III inhibitors in complex with the tyrosine kinase cSrc allowed us to employ principles of structure-based design to develop these scaffolds into potent type II kinase inhibitors. One of these compounds, 3c (RL46), disrupts FAK-mediated focal adhesions in cancer cells via direct inhibition of cSrc. Details gleaned from crystal structures revealed a key feature of a subset of these compounds, a surprising flexibility in the vicinity of the gatekeeper residue that allows these compounds to overcome a dasatinib-resistant gatekeeper mutation emerging in cSrc.

  DOI：

  10.1021/jm9002928

文献信息

• Fluorescently Or Spin-Labeled Kinases For Rapid Screening And Identification Of Novel Kinase Inhibitor Scaffolds
  申请人：Rauh Daniel

  公开号：US20110212475A1

  公开（公告）日：2011-09-01

  The present invention relates to a kinase labeled at an amino acid having a free thiol or amino group, wherein said amino acid is naturally present or introduced in the activation loop of said kinase, with (a) a thiol- or amino-reactive fluorophore sensitive to polarity changes in its environment; or (b) a thiol-reactive spin label, an isotope or an isotope-enriched thiol- or amino-reactive label, such that said fluorophore, spin label, isotope or isotope-enriched label does not inhibit the catalytic activity and does not interfere with the stability of the kinase. The invention furthermore relates to a method of screening for kinase inhibitor, a method of determining the kinetics of ligand binding and/or of dissociation of a kinase inhibitor and a method of generating mutated kinases suitable for the screening of kinase inhibitors using the kinase of the present invention.