(4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-6b-(2-methanesulfonyloxy-acetyl)-4a,6a-dimethyl-2-oxo2,4b,5,6,6a,6b,7,9,9a,10,10a,10b,11,12-tetradecahydro-4aH-8-aza-pentaleno[2,1-a]phenanthrene-8-carboxylic acid vinyl ester | 1323943-45-8

• 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: (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-6b-(2-methanesulfonyloxy-acetyl)-4a,6a-dimethyl-2-oxo2,4b,5,6,6a,6b,7,9,9a,10,10a,10b,11,12-tetradecahydro-4aH-8-aza-pentaleno[2,1-a]phenanthrene-8-carboxylic acid vinyl ester
• 英文别名: (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-Difluoro-5-hydroxy-6b-(2-methanesulfonyloxy-acetyl)-4a,6a-dimethyl-2-oxo-2,4b,5,6,6a,6b,7,9,9a,10,10a,10b,11,12-tetradecahydro-4aH-8-aza-pentaleno[2,1-a]phenanthrene-8-carboxylic acid vinyl ester；ethenyl (1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-9,13-dimethyl-8-(2-methylsulfonyloxyacetyl)-16-oxo-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-diene-6-carboxylate
• CAS: 1323943-45-8
• 化学式: C₂₇H₃₃F₂NO₈S
• 分子量: 569.624
• InChiKey: NCEIIODTKHZXJA-PTRVROEJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-6b-(2-methanesulfonyloxy-acetyl)-4a,6a-dimethyl-2-oxo2,4b,5,6,6a,6b,7,9,9a,10,10a,10b,11,12-tetradecahydro-4aH-8-aza-pentaleno[2,1-a]phenanthrene-8-carboxylic acid vinyl ester 在 盐酸 、 potassium fluoride 、 甲酸 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 8.75h， 生成 (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-8-(3,3-Dimethyl-butyl)-4b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4a,6a-dimethyl-4b,5,6,6a,6b,7,8,9,9a,10,10a,10b,11,12-tetradecahydro-4aH-8-aza-pentaleno[2,1-a]phenanthren-2-one
  参考文献：
  名称：

  PYRROLIDINE DERIVATIVES

  摘要：

  本发明涉及新型糖皮质激素系列的抗炎和抗过敏化合物，制备此类化合物的方法，包含它们的药物组合物，它们的组合和治疗用途。更具体地，本发明涉及吡咯烷衍生物的糖皮质激素。

  公开号：

  US20110201580A1
• 作为产物：
  描述：

  21-乙酰氧基-6Alpha,9Alpha二氟-11Β-羟基孕甾-1,4,16-三烯-3,20-二酮 在 碳酸氢钠 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 4.0h， 生成 (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-6b-(2-methanesulfonyloxy-acetyl)-4a,6a-dimethyl-2-oxo2,4b,5,6,6a,6b,7,9,9a,10,10a,10b,11,12-tetradecahydro-4aH-8-aza-pentaleno[2,1-a]phenanthrene-8-carboxylic acid vinyl ester
  参考文献：
  名称：

  Novel Pyrrolidine Derivatives of Budesonide as Long Acting Inhaled Corticosteroids for the Treatment of Pulmonary Inflammatory Diseases

  摘要：

  Inhaled corticosteroids (ICSs) represent the first line therapy for the treatment of asthma and are also extensively utilized in chronic obstructive pulmonary disease. Our goal was to develop a new ICS with a basic group, which can allow solid state feature modulation, achieving at the same time high local anti-inflammatory effect and low systemic exposure. Through a rational drug design approach, a new series of pyrrolidine derivatives of budesonide was identified. Within the series, several compounds showed nanomolar binding affinity (K-i) with GR that mostly correlated with the effect in inducing GR nuclear trans location in CHO cells and anti-inflammatory effects in macrophagic cell lines. Binding and functional cell-based assays allowed identifying compound 17 as a potent ICS agonist with a PK profile showing an adequate lung retention and low systemic exposure in vivo. Finally, compound 17 proved to be more potent than budesonide in a rat model of acute pulmonary inflammation.

  DOI：

  10.1021/acs.jmedchem.7b01873

文献信息

• Pyrrolidine compounds,pharmaceutical compositions containing the same, devices containing the same, and methods of treating asthma or chronic obstructive pulmonary disease by administering the same
  申请人：Ghidini Eleonora

  公开号：US08481517B2

  公开（公告）日：2013-07-09

  The present invention relates to novel anti-inflammatory and antiallergic compounds of the glucocorticosteroid series, methods of preparing such compounds, pharmaceutical compositions comprising them, combinations and therapeutic uses thereof. More particularly, the invention relates to glucocorticosteroids that are derivatives of pyrrolidine.

  本发明涉及糖皮质激素系列的新型抗炎和抗过敏化合物，制备这种化合物的方法，包含它们的药物组合物以及它们的治疗用途。更具体地说，本发明涉及吡咯烷衍生物的糖皮质激素。
• [EN] PREGNANE COMPOUNDS CONDENSED IN POSITION 16,17 WITH A PYROLIDINE RING WITH GLUCOCORTICOID ACTIVITY<br/>[FR] DÉRIVÉS DE PYRROLIDINE
  申请人：CHIESI FARMA SPA

  公开号：WO2011095535A3

  公开（公告）日：2011-11-17
• US8481517B2
  申请人：——

  公开号：US8481517B2

  公开（公告）日：2013-07-09