6-[4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeroylamino)-4-methyl-2,3-benzoxazin-1-one | 217197-00-7

• 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-methoxyphenyl)-4-methyl-2-oxo-valeroylamino)-4-methyl-2,3-benzoxazin-1-one
• 英文别名: 6-[4-(5-fluoro-2-methoxyhenyl)-4-methyl-2-oxo-valeroylamino]-4-methyl-2,3-benzoxazin-1-one；4-(5-fluoro-2-methoxyphenyl)-4-methyl-N-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-oxopentanamide
• CAS: 217197-00-7
• 化学式: C₂₂H₂₁FN₂O₅
• 分子量: 412.418
• InChiKey: DEUHAVMPRYKFAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  94.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-[4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeroylamino)-4-methyl-2,3-benzoxazin-1-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 2-benzyl-4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methylpentanoic acid (4-methyl-1-oxo-1H-benzo[d][1,2]oxazin-6-yl)amide
  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
• 作为产物：
  描述：

  2-(5-fluoro-2-methoxyphenyl)propan-2-ol 在 氢氧化钾 、 氯化亚砜 、 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-methoxyphenyl)-4-methyl-2-oxo-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

• Nonsteroidal gestagens
  申请人：Schering Aktiengesellschaft

  公开号：US06344454B1

  公开（公告）日：2002-02-05

  This invention describes the new, nonsteroidal gestagens of general formula I in which A, B, Ar, R1, R2 and R3 have the meanings that are indicated in more detail in the description. The new compounds show a very great affinity to the gestagen receptor. They can be used alone or in combination with estrogens in contraceptive preparations. In addition, they can be used for treating endometriosis. Together with estrogens, they can also be used in preparations for treating gynecological disorders, for treating premenstrual symptoms and for substitution therapy. Based on the androgenic action, they can also be used for male birth control, male HRT and hormone therapy and for treating andrological disease agents.

  本发明描述了具有一般公式 I 的新非甾体孕激素：其中 A、B、Ar、R1、R2 和 R3 的含义在描述中更详细地指出。这些新化合物对孕激素受体的亲和力非常强。它们可以单独使用，也可以与雌激素结合用于避孕制剂中。此外，它们还可以用于治疗子宫内膜异位症。与雌激素结合时，它们还可用于治疗妇科疾病、治疗经前症状和替代疗法。基于其雄激素作用，它们还可用于男性避孕、男性激素替代疗法和激素治疗，以及治疗男科疾病。
• NICHTSTEROIDALE ENTZÜNDUNGSHEMMER
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP1133486A2

  公开（公告）日：2001-09-19
• US6245804B1
  申请人：——

  公开号：US6245804B1

  公开（公告）日：2001-06-12
• US6323199B1
  申请人：——

  公开号：US6323199B1

  公开（公告）日：2001-11-27
• US6344454B1
  申请人：——

  公开号：US6344454B1

  公开（公告）日：2002-02-05