N-(2-Hydroxy-4-nitrophenyl)-N'-(2-ethylphenyl)urea

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: N-(2-Hydroxy-4-nitrophenyl)-N'-(2-ethylphenyl)urea
• 英文别名: 1-(2-hydroxy-4-nitrophenyl)-3-(2-ethylphenyl)urea；1-(2-ethylphenyl)-3-(2-hydroxy-4-nitrophenyl)urea
• 化学式: C₁₅H₁₅N₃O₄
• 分子量: 301.302
• InChiKey: PZBLZIXURGLVNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 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2-乙基苯酯 、 2-氨基-5-硝基苯酚 在 N-(2-Hydroxy-4-nitrophenyl)-N'-(2-ethylphenyl)urea 、 二氯甲烷 、 hexanes 作用下， 以afforded the title compound(0.44 g, 43%)的产率得到N-(2-Hydroxy-4-nitrophenyl)-N'-(2-ethylphenyl)urea
  参考文献：
  名称：

  IL-8 receptor antagonists

  摘要：

  本发明涉及苯基脲在治疗由趋化因子白细胞介素-8（IL-8）介导的疾病状态中的新用途。

  公开号：

  US05886044A1
• 作为试剂：
  描述：

  异氰酸2-乙基苯酯 、 2-氨基-5-硝基苯酚 在 N-(2-Hydroxy-4-nitrophenyl)-N'-(2-ethylphenyl)urea 、 二氯甲烷 、 hexanes 作用下， 以afforded the title compound (0.44 g, 43%) EI-MS m/z 302的产率得到N-(2-Hydroxy-4-nitrophenyl)-N'-(2-ethylphenyl)urea
  参考文献：
  名称：

  US06005008

  摘要：

  公开号：

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)
• Phenyl urea antagonists of the IL-8 receptor
  申请人：SmithKline Beecham Corporation

  公开号：US06211373B1

  公开（公告）日：2001-04-03

  This invention relates to novel compounds of Formula (I), and a novel use of these compounds in treating chemokine mediated diseases, wherein the chemokine binds to an IL-8 a or b receptor. Compounds of Formula (1) are represented by the structure: wherein interalia, X is oxygen or sulfur; R is any functional moiety having an ionizable hydrogen and a pKa of 10 or less; R1 is independently selected from hydrogen; halogen; nitro; cyano; C1-C10 alkyl; halosubstituted C1-10 alkyl; C2-10 alkenyl; C1-10 alkoxy; halosubstituted C1-10 alkoxy; azide; (CR8R8)qS(O)tR4; hydroxy; hydroxy substituted C1-4 alkyl; aryl; aryl C1-4 alkyl; aryl C2-10 alkenyl; aryloxy; aryl C1-4 alkyloxy; heteroaryl; heteroarylalkyl; heteroaryl C2-10 alkenyl; heteroaryl C1-4 alkyloxy; heterocyclic, heterocyclic C1-4 alkyl; heterocyclic C1-4 alkyloxy; heterocyclic C2-10 alkenyl; q is 0 or an integer having a value of 1 to 10; n is an integer having a value of 1 to 3; m is an integer having a value of 1 to 3; n is an integer having a value of 1 to 3; Y is hydrogen; halogen; nitro; cyano; halosubstituted C1-10 alkyl; C1-10 alkyl; C2-10 alkenyl; C1-10 alkoxy; halosubstituted C1-1- alkoxy; azide; (CR8R8)qS(O)tR4, (CR8R8)qOR4; hydroxy; hydroxy substituted C1-4 alkyl; aryl; aryl C1-4 alkyl; aryloxy; aryC1-4 alkyloxy; aryl C2-10 alkenyl; heteroaryl; heteroarylalkyl; heteroaryl C1-4 alkyloxy; heteroaryl C2-10 alkenyl; heterocyclic, heterocyclic C1-4 alkyl; heterocyclic C2-10 alkenyl; or a pharmaceutically acceptable salt thereof.

  本发明涉及式（I）的新化合物和这些化合物在治疗趋化因子介导的疾病方面的新用途，其中趋化因子结合到IL-8 a或b受体。式（1）的化合物由以下结构表示：其中，interalia，X是氧或硫；R是具有离子化氢和pKa小于10的任何功能基团；R1独立地选择自氢；卤素；硝基；氰基；C1-C10烷基；卤代C1-10烷基；C2-10烯基；C1-10烷氧基；卤代C1-10烷氧基；叠氮基；（CR8R8）qS（O）tR4；羟基；羟基取代的C1-4烷基；芳基；芳基C1-4烷基；芳基C2-10烯基；芳氧基；芳基C1-4烷氧基；杂芳基；杂芳基烷基；杂芳基C2-10烯基；杂芳基C1-4烷氧基；杂环，杂环C1-4烷基；杂环C1-4烷氧基；杂环C2-10烯基；q为0或具有值为1至10的整数；n为具有值为1至3的整数；m为具有值为1至3的整数；n为具有值为1至3的整数；Y是氢；卤素；硝基；氰基；卤代C1-10烷基；C1-10烷基；C2-10烯基；C1-10烷氧基；卤代C1-1-烷氧基；叠氮基；（CR8R8）qS（O）tR4，（CR8R8）qOR4；羟基；羟基取代的C1-4烷基；芳基；芳基C1-4烷基；芳氧基；芳基C1-4烷氧基；芳基C2-10烯基；杂芳基；杂芳基烷基；杂芳基C1-4烷氧基；杂芳基C2-10烯基；杂环，杂环C1-4烷基；杂环C2-10烯基；或其药学上可接受的盐。
• Structural optimization of a CXCR2-directed antagonist that indirectly inhibits γ-secretase and reduces Aβ
  作者：Pancham Bakshi、Chao Jin、Pierre Broutin、Beniam Berhane、Jon Reed、Michael Mullan

  DOI：10.1016/j.bmc.2009.09.051

  日期：2009.12

  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.
• US06180675B2
  申请人：——

  公开号：——

  公开（公告）日：——
• IL-8 RECEPTOR ANTAGONISTS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP0809492A1

  公开（公告）日：1997-12-03