ethyl 3-(2-isopropyl-4-thiazolyl)propanoate | 202817-18-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 3-(2-isopropyl-4-thiazolyl)propanoate
• 英文别名: Ethyl 3-(2-propan-2-yl-1,3-thiazol-4-yl)propanoate
• CAS: 202817-18-3
• 化学式: C₁₁H₁₇NO₂S
• 分子量: 227.327
• InChiKey: MRVOQDNMTLLXKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  67.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-(2-isopropyl-4-thiazolyl)propanoate 在 lithium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-(2-isopropyl-4-thiazolyl)propanoic acid
  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：

  2-异丙基噻唑-4-羧酸乙酯 在 甲醇 、 sodium hydride 、 二异丁基氢化铝 、 magnesium 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 1.41h， 生成 ethyl 3-(2-isopropyl-4-thiazolyl)propanoate
  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+