N-(2-羟基-4-硝基苯基)-N'-苯基脲 | 80883-76-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: N-(2-羟基-4-硝基苯基)-N'-苯基脲
• 英文名称: N-(2-Hydroxy-4-nitrophenyl)-N'-phenylurea
• 英文别名: SKF 83589；1-(2-hydroxy-4-nitrophenyl)-3-phenylurea；N-(2-Hydroxy4-nitrophenyl)-N'-phenylurea
• CAS: 80883-76-7
• 化学式: C₁₃H₁₁N₃O₄
• 分子量: 273.248
• InChiKey: SAUHQYBXEGARCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  异氰酸苯酯 、 2-氨基-5-硝基苯酚 以 四氢呋喃 为溶剂， 反应 12.0h， 以49%的产率得到N-(2-羟基-4-硝基苯基)-N'-苯基脲
  参考文献：
  名称：

  Structural optimization of a CXCR2-directed antagonist that indirectly inhibits γ-secretase and reduces Aβ

  摘要：

  Amyloid beta(A beta), a key molecule in the pathogenesis of Alzheimer's disease (AD), is derived from the amyloid precursor protein (APP) by sequential proteolysis via beta- and gamma-secretases. Because of their role in generation of A beta, these enzymes have emerged as important therapeutic targets for AD. In the case of gamma-secretase, progress has been made towards designing potent inhibitors with suitable pharmacological profiles. Direct gamma-secretase inhibitors are being evaluated in clinical trials and new strategies are being explored to block gamma-secretase activity indirectly as well. In this regard, we have previously reported an indirect regulation of gamma-secretase through antagonism of CXCR2, a G-protein coupled receptor (GPCR). We demonstrated that N-(2-hydroxy-4-nitrophenyl)-N'-(2-bromophenyl)urea (SB225002), a selective inhibitor of CXCR2 also plays a role in an indirect inhibition of gamma-secretase. Furthermore, we reported a similar to 5-fold difference in the selective inhibition of APP versus Notch processing via gamma-secretase following treatment with SB225002. Herein we describe the synthesis and optimization of SB225002. By determination of the structure-activity relationship (SAR), we derived small molecules that inhibit A beta 40 production with IC(50) values in the sub-micromolar range in a cell-based assay and also validated the potential of CXCR2 as a new target for therapeutic intervention in AD. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.051

文献信息

• [EN] IL-8 RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RECEPTEURS D'IL-8
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1996025157A1

  公开（公告）日：1996-08-22

  (EN) This invention relates to the novel use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).(FR) Cette invention se rapporte à une nouvelle utilisation des urées phényliques dans le traitement d'états pathologiques dont le médiateur est la chimiokine, appelée interleukine-8 (IL-8).

  该发明涉及苯基脲在治疗由趋化因子Interleukin-8 (IL-8)介导的疾病状态中的新用途。(中文翻译)
• IL-8 receptor antagonists
  申请人：SmithKline Beecham Corporation

  公开号：US20020128321A1

  公开（公告）日：2002-09-12

  This invention relates to novel compounds and a novel use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).

  本发明涉及新型化合物和苯基脲在治疗由趋化因子Interleukin-8（IL-8）介导的疾病状态中的新用途。
• Evaluation of Potent and Selective Small-Molecule Antagonists for the CXCR2 Chemokine Receptor
  作者：Katherine L. Widdowson、John D. Elliott、Daniel F. Veber、Hong Nie、Melvin C. Rutledge、Brent W. McCleland、Jia-Ning Xiang、Anthony J. Jurewicz、Robert P. Hertzberg、James J. Foley、Don E. Griswold、Lenox Martin、Judithann M. Lee、John R. White、Henry M. Sarau

  DOI：10.1021/jm034248l

  日期：2004.3.1

  N,N'-Diarylureas were prepared, and the structure-activity relationship relative to the CXCR2 receptor was examined. This led to the identification of a potent and highly selective CXCR2 antagonist, which in addition was shown to be functionally active both in vitro against human neutrophils and in vivo in rabbit models of ear edema and neutropenia.
• IL-8 RECEPTOR ANTAGONISTS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0809492A1

  公开（公告）日：1997-12-03
• EP0809492A4
  申请人：——

  公开号：EP0809492A4

  公开（公告）日：2007-01-24