Butanamide, 3,3-dimethyl-N-(4-nitrophenyl)- | 87315-20-6

• 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: Butanamide, 3,3-dimethyl-N-(4-nitrophenyl)-
• 英文别名: 3,3-dimethyl-N-(4-nitrophenyl)butanamide
• CAS: 87315-20-6
• 化学式: C₁₂H₁₆N₂O₃
• 分子量: 236.271
• InChiKey: WRHVCKUCNADMOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Butanamide, 3,3-dimethyl-N-(4-nitrophenyl)- 在 盐酸 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 锌 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.17h， 生成 N-[4-(3,3-dimethylbutyrylamino)phenyl]-thiazole-2-carboxamide
  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：

  3,3-二甲基丁酰氯 、 4-硝基苯胺 在 吡啶 作用下， 以 1,2-二氯乙烷 为溶剂， 以66%的产率得到Butanamide, 3,3-dimethyl-N-(4-nitrophenyl)-
  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

• Hydroxybenzylamino derivatives as anti-inflammatory agents
  申请人：Merck & Co., Inc.

  公开号：US04578390A1

  公开（公告）日：1986-03-25

  Hydroxybenzylamino derivatives have been prepared from an appropriate hydroxybenzaldehyde and an amine followed by reduction. These compounds are found to be active topical anti-inflammatory agents.

  羟基苯甲醛和胺经过还原反应，制备出羟基苯甲酰胺衍生物。这些化合物被发现具有活性的局部抗炎作用。
• Hydroxybenzylamino-aryl compounds, process for preparing and pharmaceutical compositions containing the same
  申请人：Merck & Co., Inc.

  公开号：EP0081782A1

  公开（公告）日：1983-06-22

  Hydroxybenzylaminobenzenes of structural formula (I) are disclosed wherein: R is (a) fluoro; (b) methoxy, ethoxy, n-propoxy or i-propoxy; (c) methylthio, ethylthio, n-propylthio or i-propylthio; (d) -OCH2-O; (e) -COOH; or (f) aryloxy; R1 is (a) unsubstituted or substituted phenyl; or (b) unsubstituted or substituted heteroaryl; n is 1 or 2. These compounds have been prepared from an appropriate hydroxybenzaldehyde and an amine followed by reduction. These compounds are found to be active topical anti-inflammatory agents.

  公开了结构式（I）的羟基苄氨基苯，其中：R 是 (a) 氟；(b) 甲氧基、乙氧基、正丙氧基或一丙氧基；(c) 甲硫基、乙硫基、正丙硫基或一丙硫基；(d) -OCH2-O；(e) -COOH；或 (f) 芳氧基；R1 是 (a) 未取代或取代的苯基；或 (b) 未取代或取代的杂芳基；n 是 1 或 2。 这些化合物是由适当的羟基苯甲醛和胺经过还原制备而成。 这些化合物被发现是具有活性的局部抗炎剂。
• JENSEN, N. P.;CHANG, M. N.
  作者：JENSEN, N. P.、CHANG, M. N.

  DOI：——

  日期：——
• US4578390A
  申请人：——

  公开号：US4578390A

  公开（公告）日：1986-03-25
• 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.