Lu AA47070 | 913842-25-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Lu AA47070
• 英文别名: phosphoric acid mono{2-[(E/Z)-4-(3,3-dimethylbutyrylamino)-3,5-difluorobenzoylimino]thiazol-3-ylmethyl} ester；phosphoric acid mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} ester；4-[(3,3-Dimethyl-1-oxobutyl)amino]-3,5-difluoro-N-[3-[(phosphonooxy)methyl]-2(3H)-thiazolylidene]benzamide；[2-[4-(3,3-dimethylbutanoylamino)-3,5-difluorobenzoyl]imino-1,3-thiazol-3-yl]methyl dihydrogen phosphate
• CAS: 913842-25-8
• 化学式: C₁₇H₂₀F₂N₃O₆PS
• 分子量: 463.399
• InChiKey: MSWIQSFUBYCFJE-UHFFFAOYSA-N

物化性质

• 溶解度：
  二甲基亚砜（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  154
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Lu AA47070 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.0h， 生成 N-[3-chloromethyl-3H-thiazol-2-(E/Z)ylidene]-4-(3,3-dimethylbutyrylamino)-3,5-difluorobenzamide
  参考文献：
  名称：

  Discovery of Phosphoric Acid Mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} Ester (Lu AA47070): A Phosphonooxymethylene Prodrug of a Potent and Selective hA_2A Receptor Antagonist

  摘要：

  The discovery and structure-activity relationship of a series of hA(2A) receptor antagonists is described. Compound 28 was selected from the series as a potent and selective compound and was shown to be efficacious in an in vivo model of Parkinson's disease. It had acceptable ADME properties; however, the low intrinsic solubility of this compound was limiting for its developability, because the oral bioavailability from dosing in suspension was significantly lower than the oral bioavailability from solution dosage. As a consequence, prodrugs of 28 were prepared with dramatically increased aqueous solubility. The prodrugs efficiently delivered 28 into systemic circulation, with no detectable levels of prodrug in plasma samples. From this investigation, we selected 32 (Lu AA47070), a phosphonooxymethylene prodrug of 28, as a drug candidate.

  DOI：

  10.1021/jm1008659
• 作为产物：
  描述：

  N-[3-chloromethyl-3H-thiazol-2-(E/Z)ylidene]-4-(3,3-dimethylbutyrylamino)-3,5-difluorobenzamide 在 磷酸 、 N,N-二异丙基乙胺 作用下， 以 水 、 乙腈 为溶剂， 反应 2.0h， 以40%的产率得到Lu AA47070
  参考文献：
  名称：

  Discovery of Phosphoric Acid Mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} Ester (Lu AA47070): A Phosphonooxymethylene Prodrug of a Potent and Selective hA_2A Receptor Antagonist

  摘要：

  The discovery and structure-activity relationship of a series of hA(2A) receptor antagonists is described. Compound 28 was selected from the series as a potent and selective compound and was shown to be efficacious in an in vivo model of Parkinson's disease. It had acceptable ADME properties; however, the low intrinsic solubility of this compound was limiting for its developability, because the oral bioavailability from dosing in suspension was significantly lower than the oral bioavailability from solution dosage. As a consequence, prodrugs of 28 were prepared with dramatically increased aqueous solubility. The prodrugs efficiently delivered 28 into systemic circulation, with no detectable levels of prodrug in plasma samples. From this investigation, we selected 32 (Lu AA47070), a phosphonooxymethylene prodrug of 28, as a drug candidate.

  DOI：

  10.1021/jm1008659

文献信息

• Discovery of Phosphoric Acid Mono-{2-[(<i>E</i>/<i>Z</i>)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} Ester (Lu AA47070): A Phosphonooxymethylene Prodrug of a Potent and Selective hA_2A Receptor Antagonist
  作者：Anette G. Sams、Gitte K. Mikkelsen、Mogens Larsen、Morten Langgård、Mark E. Howells、Tenna J. Schrøder、Lise T. Brennum、Lars Torup、Erling B. Jørgensen、Christoffer Bundgaard、Mads Kreilgård、Benny Bang-Andersen

  DOI：10.1021/jm1008659

  日期：2011.2.10

  The discovery and structure-activity relationship of a series of hA(2A) receptor antagonists is described. Compound 28 was selected from the series as a potent and selective compound and was shown to be efficacious in an in vivo model of Parkinson's disease. It had acceptable ADME properties; however, the low intrinsic solubility of this compound was limiting for its developability, because the oral bioavailability from dosing in suspension was significantly lower than the oral bioavailability from solution dosage. As a consequence, prodrugs of 28 were prepared with dramatically increased aqueous solubility. The prodrugs efficiently delivered 28 into systemic circulation, with no detectable levels of prodrug in plasma samples. From this investigation, we selected 32 (Lu AA47070), a phosphonooxymethylene prodrug of 28, as a drug candidate.