ethyl 5-(2-hydroxybutyl)-2-isoxazoline-3-carboxylate | 202817-14-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: ethyl 5-(2-hydroxybutyl)-2-isoxazoline-3-carboxylate
• 英文别名: Ethyl 5-(2-hydroxybutyl)-4,5-dihydro-1,2-oxazole-3-carboxylate
• CAS: 202817-14-9
• 化学式: C₁₀H₁₇NO₄
• 分子量: 215.249
• InChiKey: NHHFFPUWPXXUDI-UHFFFAOYSA-N

物化性质

• 沸点：
  304.8±34.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  68.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 5-(2-hydroxybutyl)-2-isoxazoline-3-carboxylate 在 镍 lithium aluminium tetrahydride 、 tetrafluoroboric acid 、 草酰氯 、 氢气 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 7.67h， 生成 2-乙基-6-羟甲基吡啶
  参考文献：
  名称：

  Discovery of Ritonavir, a Potent Inhibitor of HIV Protease with High Oral Bioavailability and Clinical Efficacy

  摘要：

  The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption, Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 mu M) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.

  DOI：

  10.1021/jm970636+
• 作为产物：
  描述：

  5-己烯-3-醇 、 氯代肟基乙酸乙酯 在 三乙胺 作用下， 以 乙醚 为溶剂， 以55%的产率得到ethyl 5-(2-hydroxybutyl)-2-isoxazoline-3-carboxylate
  参考文献：
  名称：

  使用腈氧化物和高烯丙醇通过环加成路线合成取代吡啶

  摘要：

  腈氧化物与未保护的高烯丙醇的环加成，然后是 Swern 氧化，产生 5-(2-氧代烷基)-2-异恶唑啉。随后在过量四氟硼酸存在下，在乙醇中对所得杂环进行 Raney Ni 还原，得到取代的吡啶衍生物。

  DOI：

  10.1246/bcsj.64.375

文献信息

• Synthesis of Substituted Pyridines by a Cycloaddition Route Using Nitrile Oxides and Homoallyl Alcohols
  作者：Shuji Kanemasa、Yoshihiko Asai、Junji Tanaka

  DOI：10.1246/bcsj.64.375

  日期：1991.2

  Cycloadditions of nitrile oxides with unprotected homoallyl alcohols, followed by Swern oxidations, lead to 5-(2-oxoalkyl)-2-isoxazolines. Subsequent Raney Ni reduction of the resulting heterocycles in ethanol in the presence of excess tetrafluoroboric acid affords substituted pyridine derivatives.

  腈氧化物与未保护的高烯丙醇的环加成，然后是 Swern 氧化，产生 5-(2-氧代烷基)-2-异恶唑啉。随后在过量四氟硼酸存在下，在乙醇中对所得杂环进行 Raney Ni 还原，得到取代的吡啶衍生物。
• KANEMASA, SHUJI;ASAI, YOSHIHIKO;TANAKA, JUNJI, BULL. CHEM. SOC. JAP., 64,(1991) N, C. 375-380
  作者：KANEMASA, SHUJI、ASAI, YOSHIHIKO、TANAKA, JUNJI

  DOI：——

  日期：——
• Discovery of Ritonavir, a Potent Inhibitor of HIV Protease with High Oral Bioavailability and Clinical Efficacy
  作者：Dale J. Kempf、Hing L. Sham、Kennan C. Marsh、Charles A. Flentge、David Betebenner、Brian E. Green、Edith McDonald、Sudthida Vasavanonda、Ayda Saldivar、Norman E. Wideburg、Warren M. Kati、Lisa Ruiz、Chen Zhao、LynnMarie Fino、Jean Patterson、Akhteruzzaman Molla、Jacob J. Plattner、Daniel W. Norbeck

  DOI：10.1021/jm970636+

  日期：1998.2.1

  The structure-activity studies leading to the potent and clinically efficacious HIV protease inhibitor ritonavir are described. Beginning with the moderately potent and orally bioavailable inhibitor A-80987, systematic investigation of peripheral (P3 and P2') heterocyclic groups designed to decrease the rate of hepatic metabolism provided analogues with improved pharmacokinetic properties after oral dosing in rats. Replacement of pyridyl groups with thiazoles provided increased chemical stability toward oxidation while maintaining sufficient aqueous solubility for oral absorption, Optimization of hydrophobic interactions with the HIV protease active site produced ritonavir, with excellent in vitro potency (EC50 = 0.02 mu M) and high and sustained plasma concentrations after oral administration in four species. Details of the discovery and preclinical development of ritonavir are described.