(1S,2S,4R,8R,9S,11S,12S,13R)-5-bromo-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-7-oxa-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-5,14,17-trien-16-one | 197845-56-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (1S,2S,4R,8R,9S,11S,12S,13R)-5-bromo-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-7-oxa-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-5,14,17-trien-16-one
• CAS: 197845-56-0
• 化学式: C₂₂H₂₆BrNO₅
• 分子量: 464.356
• InChiKey: NTAQWONTDNPNJN-YENSXTRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  96.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S,2S,4R,8R,9S,11S,12S,13R)-5-bromo-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-7-oxa-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-5,14,17-trien-16-one 在 4-甲基苯磺酸吡啶 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 121.25h， 生成 (4aR,4bS,5S,6aS,6bR,9aR,10aS,10bS)-5-Hydroxy-6b-(2-hydroxy-acetyl)-9-methoxy-4a,6a-dimethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-7-oxa-8-aza-pentaleno[2,1-a]phenanthren-2-one
  参考文献：
  名称：

  Studies towards the synthesis of 16α-carboxyprednisolones. Chemistry of fused bromoisoxazolines

  摘要：

  Bromonitrile-N-oxide adds to the enone 9b/c completely regio-and stereoselectively to form the bromoisoxazoline 10b/c. The latter can be transformed into the nitrile 11, previously hydrolyzed(14) to the target 16 alpha-carbomethoxyprednisolone 4a a potentially locally active antiinflammatory steroid. The methoxyisoxazoline 12, prepared from 10b has proved surprisingly resistant to reductive cleavage of the N-O bond. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00983-6
• 作为产物：
  描述：

  1,1-二溴甲醛肟 、 脱氧强的松龙-16-烯 在 碳酸氢钠 作用下， 以 乙酸乙酯 为溶剂， 反应 6.0h， 以100%的产率得到(1S,2S,4R,8R,9S,11S,12S,13R)-5-bromo-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-7-oxa-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-5,14,17-trien-16-one
  参考文献：
  名称：

  Studies towards the synthesis of 16α-carboxyprednisolones. Chemistry of fused bromoisoxazolines

  摘要：

  Bromonitrile-N-oxide adds to the enone 9b/c completely regio-and stereoselectively to form the bromoisoxazoline 10b/c. The latter can be transformed into the nitrile 11, previously hydrolyzed(14) to the target 16 alpha-carbomethoxyprednisolone 4a a potentially locally active antiinflammatory steroid. The methoxyisoxazoline 12, prepared from 10b has proved surprisingly resistant to reductive cleavage of the N-O bond. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00983-6

文献信息

• Discovery of a novel isoxazoline derivative of prednisolone endowed with a robust anti-inflammatory profile and suitable for topical pulmonary administration
  作者：E. Ghidini、A.M. Capelli、C. Carnini、V. Cenacchi、G. Marchini、A. Virdis、A. Italia、F. Facchinetti

  DOI：10.1016/j.steroids.2014.12.016

  日期：2015.3

  A novel glucocorticoids series of (GCs), 6 alpha,9 alpha-di-Fluoro 3-substituted C-16,17-isoxazolines was designed, synthesised and their structure activity relationship was evaluated with glucocorticoid receptor (GR) binding studies together with GR nuclear translocation cell-based assays. This strategy, coupled with in silica modelling analysis, allowed for the identification of Cpd #15, an isoxazoline showing a sub-nanomolar inhibitory potency (IC50 = 0.84 nM) against TNF alpha-evoked IL-8 release in primary human airways smooth muscle cells. In Raw264.7 mouse macrophages, Cpd #15 inhibited LPS-induced NO release with a potency (IC50 = 6 nM) > 10-fold higher with respect to Dexamethasone. Upon intratracheal (it.) administration, Cpd #15, at 0.1 mu mol/kg significantly inhibited and at 1 mu mol/kg fully counteracted eosinophilic infiltration in a model of allergen-induced pulmonary inflammation in rats. Moreover, Cpd #15 proved to be suitable for pulmonary topical administration given its sustained lung retention (t(1/2) = 6.5 h) and high pulmonary levels (>100-fold higher than plasma levels) upon intratracheal administration in rats. In summary, Cpd #15 displays a pharmacokinetic and pharmacodynamic profile suitable for topical treatment of conditions associated with pulmonary inflammation such as asthma and COPD. (C) 2015 Elsevier Inc. All rights reserved.