3-(dimethylamino)-5-ethyl-6-methyl-4-[3-[(Z)-styryl]benzoyl]-1H-pyridin-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 3-(dimethylamino)-5-ethyl-6-methyl-4-[3-[(Z)-styryl]benzoyl]-1H-pyridin-2-one
• 英文别名: 3-(dimethylamino)-5-ethyl-6-methyl-4-[3-[(Z)-2-phenylethenyl]benzoyl]-1H-pyridin-2-one
• 化学式: C₂₅H₂₆N₂O₂
• 分子量: 386.494
• InChiKey: HWBIRXAROAGGGQ-PFONDFGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-(dimethylamino)-5-ethyl-4-[3-(hydroxymethyl)benzoyl]-6-methyl-1H-pyridin-2-one 在 氯化亚砜 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 50.67h， 生成 3-(dimethylamino)-5-ethyl-6-methyl-4-[3-[(Z)-styryl]benzoyl]-1H-pyridin-2-one
  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

文献信息

• 4-Benzyl- and 4-Benzoyl-3-dimethylaminopyridin-2(1<i>H</i>)-ones, a New Family of Potent Anti-HIV Agents:  Optimization and in Vitro Evaluation against Clinically Important HIV Mutant Strains
  作者：Abdellah Benjahad、Karine Courté、Jérôme Guillemont、Dominique Mabire、Sophie Coupa、Alain Poncelet、Imre Csoka、Koen Andries、Rudi Pauwels、Marie-Pierre de Béthune、Claude Monneret、Emile Bisagni、Chi Hung Nguyen、David S. Grierson

  DOI：10.1021/jm0407658

  日期：2004.10.1

  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.