2-cyclohexylmethyl-4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methylpentanoic acid (4-methyl-1-oxo-1H-benzo[d][1,2]oxazin-6-yl)amide

• 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: 2-cyclohexylmethyl-4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methylpentanoic acid (4-methyl-1-oxo-1H-benzo[d][1,2]oxazin-6-yl)amide
• 英文别名: 2-(cyclohexylmethyl)-4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-N-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)pentanamide
• 化学式: C₂₈H₃₃FN₂O₅
• 分子量: 496.579
• InChiKey: LVZOQUMLGOHFGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  7

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-cyclohexylmethyl-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

文献信息

• Novel flavanoids as chemotherapeutic, chemopreventive, and antiangiogenic agents
  申请人：——

  公开号：US20040029914A1

  公开（公告）日：2004-02-12

  Novel compounds are useful as chemotherapeutic, chemopreventative, and antiangiogenic agents are provided. The compounds are flavanoids, including flavanones, flavanols, and chalcones. The compounds have the structure of formula (I) 1 wherein R 1 through R 3 and R 5 through R 11 are defined herein, and &agr;, &bgr;, and &ggr; are optional bonds, providing that when &agr; is absent, &bgr; is present, and when &bgr; is absent, &agr; is present. When &agr; is present, preferred R 4 moieties are selected from O, S, NH and CH 2 , and when &agr; is absent, preferred R 4 groups are selected from OH, SH, NH 2 and CH 3 . When &ggr; is present, the preferred R 5 substituent is O, while when &ggr; is absent, the preferred R 5 substituent is OH. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.

  提供了作为化疗、化学预防和抗血管生成药物的有用的新化合物。这些化合物是黄酮类化合物，包括黄酮醇、黄酮醇和香豆素。这些化合物具有公式(I)的结构，其中R1至R3和R5至R11如本文所定义，α、β和γ是可选键，当α不存在时，β存在，当β不存在时，α存在。当α存在时，首选的R4基团选自O、S、NH和CH2，当α不存在时，首选的R4基团选自OH、SH、NH2和CH3。当γ存在时，首选的R5取代基为O，而当γ不存在时，首选的R5取代基为OH。还提供了药物组合物，以及合成和使用方法。
• COMPOSITIONS AND METHODS FOR TREATING, CONTROLLING, REDUCING, OR AMELIORATING INFLAMMATORY PAIN
  申请人：Ward Keith W.

  公开号：US20120316199A1

  公开（公告）日：2012-12-13

  A composition for treating, controlling, reducing, or ameliorating inflammatory pain comprises a dissociated glucocorticoid receptor agonist (“DIGRA”), a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester thereof. The composition can comprise an additional anti-inflammatory agent and can be formulated for topical application, injection, or implantation. It may be used in a method of managing post-surgical ocular pain such that it has lower risk of eliciting adverse side effects seen with other therapeutic agents.

  用于治疗、控制、减轻或改善炎症性疼痛的组合物包括解离型糖皮质激素受体激动剂（“DIGRA”）、其前药、其药学上可接受的盐或其药学上可接受的酯。该组合物可以包含额外的抗炎药物，并可制成局部应用、注射或植入剂。它可以用于管理术后眼部疼痛的方法，从而降低与其他治疗剂产生的不良副作用风险。
• 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。
• Compositions and methods for treating or preventing glaucoma or progression thereof
  申请人：BAUSCH & LOMB INCORPORATED

  公开号：EP2397140A1

  公开（公告）日：2011-12-21

  A composition for treating or preventing glaucoma or its progression comprises a dissociated glucocorticoid receptor agonist ("DIGRA"), a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester thereof. The composition can comprise an additional anti-inflammatory agent and can be formulated for topical application, injection, or implantation. It may be used in combination with another therapy directed to reducing intraocular pressure.

  一种用于治疗或预防青光眼或青光眼进展的组合物包含一种离体糖皮质激素受体激动剂（"DIGRA"）、其原药、其药学上可接受的盐或其药学上可接受的酯。该组合物可包含一种额外的抗炎剂，并可配制成外用、注射或植入剂。它可与另一种降低眼内压的疗法联合使用。
• 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