3-{(2S)-4-(2,5-difluorophenyl)-1-[(2S)-2-hydroxy-3,3-dimethylbutanoyl]-2,5-dihydro-1H-pyrrol-2-yl}phenyl dihydrogen phosphate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 3-{(2S)-4-(2,5-difluorophenyl)-1-[(2S)-2-hydroxy-3,3-dimethylbutanoyl]-2,5-dihydro-1H-pyrrol-2-yl}phenyl dihydrogen phosphate
• 英文别名: 3-{(2S)-4-(2,5-difluorophenyl)-1-[(2S)-2-hydroxy-3,3-dimethylbutanoyl]2,5-dihydro-1H-pyrro1-2-yl}phenyl dihydrogen phosphate；[3-[(2S)-4-(2,5-difluorophenyl)-1-[(2S)-2-hydroxy-3,3-dimethylbutanoyl]-2,5-dihydropyrrol-2-yl]phenyl] dihydrogen phosphate
• 化学式: C₂₂H₂₄F₂NO₆P
• 分子量: 467.406
• InChiKey: PKYLTOJBBHOYBN-VQTJNVASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (S)-(-)-2-羟基-3,3-二甲基丁酸 在 palladium on activated charcoal 四氯化碳 、 4-二甲氨基吡啶 、 二乙基异丙基胺 、 1,4-环己二烯 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 3-{(2S)-4-(2,5-difluorophenyl)-1-[(2S)-2-hydroxy-3,3-dimethylbutanoyl]-2,5-dihydro-1H-pyrrol-2-yl}phenyl dihydrogen phosphate
  参考文献：
  名称：

  Kinesin spindle protein (KSP) inhibitors. Part 3: Synthesis and evaluation of phenolic 2,4-diaryl-2,5-dihydropyrroles with reduced hERG binding and employment of a phosphate prodrug strategy for aqueous solubility

  摘要：

  2,4-Diaryl-2,5-dihydropyrroles have been discovered to be novel, potent and water-soluble inhibitors of KSP, an emerging therapeutic target for the treatment of cancer. A potential concern for these basic KSP inhibitors (1 and 2) was hERG binding that can be minimized by incorporation of a potency-enhancing C2 phenol combined with neutral N1 side chains. Aqueous solubility was restored to these, and other, non-basic inhibitors, through a phosphate prodrug strategy. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.094

文献信息

• Prodrugs of mitotic kinesin inhibitors
  申请人：Fraley E. Mark

  公开号：US20060135594A1

  公开（公告）日：2006-06-22

  The present invention relates to phosphate ester prodrugs of dihydropyrrole compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

  本发明涉及磷酸酯前药二氢吡咯烷化合物，用于治疗细胞增殖性疾病、治疗与KSP动力蛋白活性相关的疾病，以及抑制KSP动力蛋白。该发明还涉及包含这些化合物的组合物，以及利用它们治疗哺乳动物癌症的方法。
• EP1636182A4
  申请人：——

  公开号：EP1636182A4

  公开（公告）日：2008-09-03
• PRODRUGS OF MITOTIC KINESIN INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1636182A2

  公开（公告）日：2006-03-22
• US7329762B2
  申请人：——

  公开号：US7329762B2

  公开（公告）日：2008-02-12
• [EN] PRODRUGS OF MITOTIC KINESIN INHIBITORS<br/>[FR] PROMEDICAMENTS D'INHIBITEURS DE KINESINE MITOTIQUE
  申请人：MERCK & CO INC

  公开号：WO2004111193A2

  公开（公告）日：2004-12-23

  The present invention relates to phosphate ester prodrugs of dihydropyrrole compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.