2-benzyl-4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methylpentanoic acid (1-oxo-1,3-dihydroisobenzofuran-5-yl)amide

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 2-benzyl-4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methylpentanoic acid (1-oxo-1,3-dihydroisobenzofuran-5-yl)amide
• 英文别名: 2-benzyl-4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-N-(1-oxo-3H-2-benzofuran-5-yl)pentanamide
• 化学式: C₂₇H₂₆FNO₅
• 分子量: 463.506
• InChiKey: KGFMFEQQZNKWLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 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 2-benzyl-4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methylpentanoic acid (1-oxo-1,3-dihydroisobenzofuran-5-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

文献信息

• Glucocorticoid mimetics, methods of making them, pharmaceutical formulations, and uses thereof
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US20030232823A1

  公开（公告）日：2003-12-18

  A compound of Formula (I) 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as defined herein, or a tautomer, prodrug, solvate, or salt thereof, pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

  一种化合物，其化学式为（I）1，其中R1、R2、R3、R4、R5和R6如本文所定义，或其互变异构体、前药、溶剂化合物或盐，包含这种化合物的药物组合物，以及使用这些化合物调节糖皮质激素受体功能的方法，以及使用这些化合物治疗由糖皮质激素受体功能介导的疾病状态或条件，或由炎症、过敏或增生过程特征的患者的方法。
• Compositions and methods for treating, controlling, reducing, or ameliorating infections and sequelae thereof
  申请人：BAUSCH & LOMB INCORPORATED

  公开号：EP2364707A2

  公开（公告）日：2011-09-14

  A composition for treating, controlling, reducing, ameliorating, or alleviating infections and their inflammatory sequelae comprises a dissociated glucocorticoid receptor agonist ('DIGRA') and an anti-infective agent, such as an antibacterial, antiviral, antifungal, antiprotozoal agent, or a combination thereof. The composition can be formulated for topical application, injection, or implantation.

  一种用于治疗、控制、减少、改善或减轻感染及其炎症后遗症的组合物包含一种解离糖皮质激素受体激动剂（"DIGRA"）和一种抗感染剂，如抗菌剂、抗病毒剂、抗真菌剂、抗原虫剂或其组合。该组合物可配制成外用、注射或植入剂。
• GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL FORMULATIONS CONTAINING THEM, AND USES THEREOF
  申请人：Boehringer Ingelheim Pharmaceuticals Inc.

  公开号：EP1467982B1

  公开（公告）日：2006-11-22
• TREATING INFECTIONS AND SEQUELAE THEREOF WITH COMBINED DISSOCIATED GLUCOCORTICOID RECEPTOR AGONISTS AND ANTI-INFECTIVE AGENTS
  申请人：Bausch & Lomb Incorporated

  公开号：EP2049112B1

  公开（公告）日：2012-03-14
• COMPOSITIONS AND METHODS FOR TREATING, REDUCING, AMELIORATING, OR ALLEVIATING POSTERIOR-SEGMENT OPHTHALMIC DISEASES
  申请人：Bausch & Lomb Incorporated

  公开号：EP2051710B1

  公开（公告）日：2011-11-02