tert-butyl 4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)phenylcarbamate | 925899-74-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)phenylcarbamate
• 英文别名: tert-butyl {4-[3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)ureido]phenyl}carbamate；tert-butyl N-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]phenyl]carbamate
• CAS: 925899-74-7
• 化学式: C₂₆H₃₃N₅O₃
• 分子量: 463.58
• InChiKey: CSIAUDJFYWILCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  97.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)phenylcarbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 1-(4-aminophenyl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea hydrochloride
  参考文献：
  名称：

  Pyrazole Derivatives Having Tyrosine Kinase Activity

  摘要：

  化合物的结构式（I）中，其中R、X、R1、R2、R3和R4的含义如权利要求项（1）所示，能够抑制酪氨酸激酶，特别是TIE-2和Raf激酶，并可用于治疗肿瘤。

  公开号：

  US20080207647A1
• 作为产物：
  描述：

  2,2,2-三氯乙基 3-叔丁基-1-(4-甲基苯基)-1H-吡唑-5-基氨基甲酸酯 、 特定基氨基甲酸脂酶 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 3.17h， 以96%的产率得到tert-butyl 4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)phenylcarbamate
  参考文献：
  名称：

  Development of a Fluorescent-Tagged Kinase Assay System for the Detection and Characterization of Allosteric Kinase Inhibitors

  摘要：

  Kinase disregulation disrupts the intricate network of intracellular signaling pathways and contributes to the onset of diseases such as cancer. Although several kinase inhibitors are on the market, inhibitor selectivity and drug resistance mutations persist as fundamental challenges in the development of effective long-term treatments. Chemical entities binding to less conserved allosteric sites would be expected to offer new opportunities for scaffold development. Because no high-throughput method was previously available, we developed a fluorescence-based kinase binding assay for identifying and characterizing ligands which stabilize the inactive kinase conformation. Here, we present a description of the development and validation of this assay using the serine/threonine kinase p38alpha. By covalently attaching fluorophores to the activation loop of the kinase, we were able to detect conformational changes and measure the K(d), k(on), and k(off) associated with the binding and dissociation of ligands to the allosteric pocket. We report the SAR of a synthesized focused library of pyrazolourea derivatives, a scaffold known to bind with high affinity to the allosteric pocket of p38alpha. Additionally, we used protein X-ray crystallography together with our assay to examine the binding and dissociation kinetics to characterize potent quinazoline- and quinoline-based type II inhibitors, which also utilize this binding pocket in p38alpha. Last, we identified the b-Raf inhibitor sorafenib as a potent low nanomolar inhibitor of p38alpha and used protein X-ray crystallography to confirm a unique binding mode to the inactive kinase conformation.

  DOI：

  10.1021/ja902010p

文献信息

• US7662827B2
  申请人：——

  公开号：US7662827B2

  公开（公告）日：2010-02-16