(2S,3S,5S)-5-carbonyl>valinyl>amino>-2-carbonyl>amino>-1,6-diphenyl-3-hydroxyhexane

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3S,5S)-5-carbonyl>valinyl>amino>-2-carbonyl>amino>-1,6-diphenyl-3-hydroxyhexane
• 英文别名: Pyridin-3-ylmethyl ((1S,2S,4S)-4-{[(2S)-2-({[(6-aminopyridin-3-yl)methoxy]carbonyl}amino)-3-methylbutanoyl]amino}-1-benzyl-2-hydroxy-5-phenylpentyl)carbamate；pyridin-3-ylmethyl N-[(2S,3S,5S)-5-[[(2S)-2-[(6-aminopyridin-3-yl)methoxycarbonylamino]-3-methylbutanoyl]amino]-3-hydroxy-1,6-diphenylhexan-2-yl]carbamate
• 化学式: C₃₇H₄₄N₆O₆
• 分子量: 668.793
• InChiKey: FETJDIXLZFVMEN-SUGCFTRWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  49
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  178
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  6-氨基烟酸甲酯 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 lithium hydroxide 、 lithium aluminium tetrahydride 、 N-ethyl-N’-(diethylaminopropyl)-carbodiimide 、 1-羟基苯并三唑一水物 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 6.0h， 生成 (2S,3S,5S)-5-carbonyl>valinyl>amino>-2-carbonyl>amino>-1,6-diphenyl-3-hydroxyhexane
  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+