isopropyl 4-(5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-2-hydroxy-4-oxobut-2-enoate | 1338973-31-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: isopropyl 4-(5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-2-hydroxy-4-oxobut-2-enoate
• CAS: 1338973-31-1
• 化学式: C₂₆H₂₂F₃NO₅
• 分子量: 485.46
• InChiKey: YNPUHEUJADFEFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.48
• 重原子数：
  35.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  85.6
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  (2,4-difluorophenyl)(6-methoxypyridin-3-yl)methanol 在 盐酸 、 三乙基硅烷 、 bis-triphenylphosphine-palladium(II) chloride 、 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 sodium hydride 、 sodium iodide 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 39.25h， 生成 isopropyl 4-(5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-2-hydroxy-4-oxobut-2-enoate
  参考文献：
  名称：

  Discovery of a Potent HIV Integrase Inhibitor That Leads to a Prodrug with Significant anti-HIV Activity

  摘要：

  Worldwide research efforts in drug discovery involving HIV integrase have produced only one compound, raltegravir, that has been approved for clinical use in HIV/AIDS. As resistance, toxicity, and drug-drug interactions are recurring issues with all classes of anti-HIV drugs, the discovery of novel integrase inhibitors remains a significant scientific challenge. We have designed a lead HIV-1 strand transfer (ST) inhibitor (IC(50) 70 nM), strategically assembled on a pyridinone scaffold. A focused structure-activity investigation of this parent compound led to a significantly more potent ST inhibitor, 2 (IC(50) 6 +/- 3 nM). Compound 2 exhibits good stability in pooled human liver microsomes. It also displays a notably favorable profile with respect to key human cytochrome P450 (CYP) isozymes and human UDP glucuronosyl transferases (UGTs). The prodrug of inhibitor 2, i.e., compound 10, was found to possess remarkable anti-HIV-1 activity in cell culture (EC(50) 9 +/- 4 nM, CC(50) 135 +/- 7 mu M, therapeutic index = 15 000).

  DOI：

  10.1021/ml2001246