N-[4-[[3-(1,3)dioxolan-2-ylbenzoyl]hydroxymethyl]-5-ethyl-2-methoxy-6-methylpyridin-3-yl]-2,2-dimethylpropionamide | 796863-78-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[4-[[3-(1,3)dioxolan-2-ylbenzoyl]hydroxymethyl]-5-ethyl-2-methoxy-6-methylpyridin-3-yl]-2,2-dimethylpropionamide
• 英文别名: N-[4-[3-(1,3-dioxolan-2-yl)benzoyl]-5-ethyl-2-methoxy-6-methylpyridin-3-yl]-2,2-dimethylpropanamide
• CAS: 796863-78-0
• 化学式: C₂₄H₃₀N₂O₅
• 分子量: 426.513
• InChiKey: LFUUYWAPNHXQMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  86.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[4-[[3-(1,3)dioxolan-2-ylbenzoyl]hydroxymethyl]-5-ethyl-2-methoxy-6-methylpyridin-3-yl]-2,2-dimethylpropionamide 在 盐酸 、 氯化亚砜 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 5.5h， 生成 ethyl (2E,4E)-5-[3-(5-amino-3-ethyl-2-methyl-6-oxo-1H-pyridine-4-carbonyl)phenyl]penta-2,4-dienoate
  参考文献：
  名称：

  4-Benzyl- and 4-Benzoyl-3-dimethylaminopyridin-2(1H)-ones, a New Family of Potent Anti-HIV Agents:  Optimization and in Vitro Evaluation against Clinically Important HIV Mutant Strains

  摘要：

  The 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 13 and 14 are representatives of a new class of highly potent non nucleoside type inhibitors of HIV-1 reverse transcriptase. To conduct SAR studies on these two lead compounds, 102 new analogues were prepared. Thirty-three compounds displayed nanomolar range activity in vitro against wild-type HIV-1, and among these, 18 were active against the 103N, Y181C, and Y188L mutant strains with IC50 values inferior to 1 muM. Evaluation of this group of analogues against an additional eight single [100I, 101E, 106A, 138K, 179E, 190A, 190S, 227C] and four double HIV mutant strains [100I + 103N, 101E + 103N, 103N + 181C, and 227L + 106A], which are often present in HIV infected patients, permitted the selection of eight compounds, 17x, 18b, 18c, 18f, 18g, 27, 30, and 42, which are globally more active than the lead molecules 13/14, emivirine and the currently used NNRTI, nevirapine. Further comparison of the 3'-CN-substituted benzoylpyridinone compound 18c, and the corresponding 3'-acrylonitrile-substituted analogue 30, to efavirenz, the reference molecule in anti-HIV therapy today, revealed that the pyridinone analogues displayed a superior inhibition profile in the in vitro cellular assay system. These results form a solid basis for continued optimization of the pyridinone series.

  DOI：

  10.1021/jm0407658
• 作为产物：
  描述：

  5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine 在 potassium permanganate 、 正丁基锂 、 四甲基乙二胺 、 三(3,6-二氧杂庚基)胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 N-[4-[[3-(1,3)dioxolan-2-ylbenzoyl]hydroxymethyl]-5-ethyl-2-methoxy-6-methylpyridin-3-yl]-2,2-dimethylpropionamide
  参考文献：
  名称：

  4-Benzyl- and 4-Benzoyl-3-dimethylaminopyridin-2(1H)-ones, a New Family of Potent Anti-HIV Agents:  Optimization and in Vitro Evaluation against Clinically Important HIV Mutant Strains

  摘要：

  The 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 13 and 14 are representatives of a new class of highly potent non nucleoside type inhibitors of HIV-1 reverse transcriptase. To conduct SAR studies on these two lead compounds, 102 new analogues were prepared. Thirty-three compounds displayed nanomolar range activity in vitro against wild-type HIV-1, and among these, 18 were active against the 103N, Y181C, and Y188L mutant strains with IC50 values inferior to 1 muM. Evaluation of this group of analogues against an additional eight single [100I, 101E, 106A, 138K, 179E, 190A, 190S, 227C] and four double HIV mutant strains [100I + 103N, 101E + 103N, 103N + 181C, and 227L + 106A], which are often present in HIV infected patients, permitted the selection of eight compounds, 17x, 18b, 18c, 18f, 18g, 27, 30, and 42, which are globally more active than the lead molecules 13/14, emivirine and the currently used NNRTI, nevirapine. Further comparison of the 3'-CN-substituted benzoylpyridinone compound 18c, and the corresponding 3'-acrylonitrile-substituted analogue 30, to efavirenz, the reference molecule in anti-HIV therapy today, revealed that the pyridinone analogues displayed a superior inhibition profile in the in vitro cellular assay system. These results form a solid basis for continued optimization of the pyridinone series.

  DOI：

  10.1021/jm0407658