6-[4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-4-methyl-2,3-benzoxazin-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-[4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-4-methyl-2,3-benzoxazin-1-one
• 英文别名: (+/-)-6-[4-(5-Fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)valeroylamino]-4-methyl-2,3-benzoxazin-1-one；4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-N-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-(trifluoromethyl)pentanamide
• 化学式: C₂₂H₂₀F₄N₂O₅
• 分子量: 468.405
• InChiKey: NLPNUYHHRWOSGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-[4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-4-methyl-2,3-benzoxazin-1-one 、 硝酸 、 碳酸氢钠 在 二氯甲烷 、 silica gel 、 ethyl acetate n-hexane 、 异丙醚 、 (-)-6-[4-(5-Fluoro-2-hydroxy-3-nitrophenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)valeroyl-amino]-4-methyl-2,3-benzoxazin-1-one 作用下， 以 乙酸乙酯 、 三氟乙酸 为溶剂， 反应 5.5h， 生成 (-)-6-[4-(5-Fluoro-2-hydroxy-3-nitrophenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)valeroyl-amino]-4-methyl-2,3-benzoxazin-1-one
  参考文献：
  名称：

  Nonsteroidal antiinflammatory agents

  摘要：

  本发明涉及一般式I1的化合物及其用于制备治疗和预防与炎症、过敏和/或增生过程相关的疾病的药物的应用。

  公开号：

  US20040209875A1
• 作为产物：
  描述：

  2-(5-fluoro-2-methoxyphenyl)propan-2-ol 在 氢氧化钾 、 氯化亚砜 、 三溴化硼 、 四氯化锡 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 生成 6-[4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-4-methyl-2,3-benzoxazin-1-one
  参考文献：
  名称：

  Trifluoromethyl group as a pharmacophore: Effect of replacing a CF3 group on binding and agonist activity of a glucocorticoid receptor ligand

  摘要：

  Compound 1, a potent glucocorticoid receptor ligand, contains a quaternary carbon bearing trifluoromethyl and hydroxyl groups. This paper describes the effect of replacing the trifluoromethyl group on binding and agonist activity of the GR ligand 1. The results illustrate that replacing the CF3 group with a cyclohexylmethyl or benzyl group maintains the GR binding potency. These substitutions alter the functional behavior of the GR ligands from agonists to antagonists. Docking studies suggest that the benzyl analog 19 binds in a similar fashion as the GR antagonist, RU486. The central benzyl group of 19 and the C-11 dimethylaniline moiety of RU486 overlay. Binding of compound 19 is believed to force helix 12 to adopt an open conformation and this leads to the antagonist properties of the non-CF3 ligands carrying a large group at the center of the molecule. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.025

文献信息

• NICHTSTEROIDALE ENTZÜNDUNGSHEMMER
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP1133486A2

  公开（公告）日：2001-09-19
• Structure of a glucocorticoid receptor ligand binding domain comprising an expanded binding pocket and methods employing same
  申请人：Bledsoe K. Randy

  公开号：US20070020684A1

  公开（公告）日：2007-01-25

  A solved three-dimensional crystal structure of a glucocorticord receptor (GR) α ligand binding domain polypeptide is disclosed, in the form of a crystalline glucocorticord receptor α ligand binding domain polypeptide in complex with the ligand fluticasone propionate (FP) and a peptide derived from the co-activator TIF2. The GR/FP/TIF2 structure includes an expanded binding pocket not seen in other GR structures. Methods of designing steroid and non-steroid modulators of the biological activity of GR and other nuclear receptors (NRs) are also disclosed. In another aspect of the present invention homology models of androgen receptor (AR), progesterone receptor (PR) and mineralcorticoid receptor (MR) are disclosed, as well as methods of forming homology models for other NRs. Methods of forming a soluble GR/FP/TIF2 complex are also disclosed.
• US6323199B1
  申请人：——

  公开号：US6323199B1

  公开（公告）日：2001-11-27
• US7112584B2
  申请人：——

  公开号：US7112584B2

  公开（公告）日：2006-09-26
• [DE] NICHTSTEROIDALE ENTZÜNDUNGSHEMMER<br/>[EN] NONSTEROIDAL ANTIINFLAMMATORIES<br/>[FR] INHIBITEURS D'INFLAMMATION NON STEROIDIQUES
  申请人：SCHERING AG

  公开号：WO2000032584A2

  公开（公告）日：2000-06-08

  Die vorliegende Erfindung beschreibt die Verwendung der allgemeinen Formel (I), worin A, B, A, Ar, R1, R2 sowie R3 die in der Beschreibung näher angegebene Bedeutung haben, zur Herstellung von Arzneimitteln mit entzündungshemmender Wirksamkeit. Die Verbindungen der allgemeinen Formel (I) zeigen eine deutliche Dissoziation zwischen anti-inflammatorischen und metabolischen Wirkungen.