(4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-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 hydrochloride | 1323943-46-9

• 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-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 hydrochloride
• 英文别名: (1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-8-(2-fluoroacetyl)-11-hydroxy-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one;hydrochloride
• CAS: 1323943-46-9
• 化学式: C₂₃H₂₈F₃NO₃*ClH
• 分子量: 459.936
• InChiKey: AABYSDACZGLQMC-VHJGTGPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.08
• 重原子数：
  31
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  66.4
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-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 hydrochloride 、 2-(三甲基硅)苯基三氟甲烷磺酸盐 在 水 、 cesium fluoride 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以28%的产率得到(4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-(2-fluoro-acetyl)-5-hydroxy-4a,6a-dimethyl-8-phenyl-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：

  根据式(I)和(I′)的新型抗炎和抗过敏化合物属于糖皮质类固醇系列，对预防和/或治疗涉及炎症细胞数量、活性和运动的疾病有效。

  公开号：

  US20130035320A1
• 作为产物：
  描述：

  二氟泼尼酯杂质11 在 盐酸 、 碳酸氢钠 、 甲基磺酰氯 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 12.5h， 生成 (4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-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 hydrochloride
  参考文献：
  名称：

  PYRROLIDINE DERIVATIVES

  摘要：

  根据式(I)和(I′)的新型抗炎和抗过敏化合物属于糖皮质类固醇系列，对预防和/或治疗涉及炎症细胞数量、活性和运动的疾病有效。

  公开号：

  US20130035320A1

文献信息

• [EN] ANTI -INFLAMMATORY STEROIDS CONDENSED IN POSITION 16,17 WITH PYRROLIDINE RING<br/>[FR] STÉROÏDES ANTI-INFLAMMATOIRES CONDENSÉS EN POSITION 16,17 AVEC UN CYCLE PYRROLIDINE
  申请人：CHIESI FARMA SPA

  公开号：WO2013017374A1

  公开（公告）日：2013-02-07

  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.

  本发明涉及糖皮质类固醇系列的新型抗炎和抗过敏化合物，以及制备这些化合物的方法、包含它们的药物组合物、以及它们的联合和治疗用途。更具体地说，该发明涉及是吡咯烷衍生物的糖皮质类固醇。
• 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
• Novel Pyrrolidine Derivatives of Budesonide as Long Acting Inhaled Corticosteroids for the Treatment of Pulmonary Inflammatory Diseases
  作者：Eleonora Ghidini、Gessica Marchini、Anna Maria Capelli、Chiara Carnini、Valentina Cenacchi、Alessandro Fioni、Fabrizio Facchinetti、Fabio Rancati

  DOI：10.1021/acs.jmedchem.7b01873

  日期：2018.6.14

  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.
• US8481517B2
  申请人：——

  公开号：US8481517B2

  公开（公告）日：2013-07-09