dimethylthiocarbamic acid O-(8-benzoyl-4-methyl-2-oxo-2H-chromen-7-yl) ester | 1207520-87-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: dimethylthiocarbamic acid O-(8-benzoyl-4-methyl-2-oxo-2H-chromen-7-yl) ester
• 英文别名: O-(8-benzoyl-4-methyl-2-oxochromen-7-yl) N,N-dimethylcarbamothioate
• CAS: 1207520-87-3
• 化学式: C₂₀H₁₇NO₄S
• 分子量: 367.425
• InChiKey: OBEWILXHIUZQKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  87.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethylthiocarbamic acid O-(8-benzoyl-4-methyl-2-oxo-2H-chromen-7-yl) ester 以 均三甲苯 为溶剂， 反应 2.0h， 以65%的产率得到dimethylthiocarbamic acid S-(8-benzoyl-4-methyl-2-oxo-2H-chromen-7-yl) ester
  参考文献：
  名称：

  Anti-Influenza Drug Discovery: Structure−Activity Relationship and Mechanistic Insight into Novel Angelicin Derivatives

  摘要：

  By using a cell-based high throughput screening campaign,a novel angelicin derivative 6a was identified to inhibit influenza A (H1N1) virus induced Cytopathic effect in Madin-Darby canine kidney cell culture in low micromolar range. Detailed structure-activity relationship studies of 6a revealed that the angelicin scaffold is essential for activity in pharmacophore B, while meta-substituted phenyl/2-thiophene rings are optimal ill pharmacophore A and C. The optimized lead 4-methyl-9-phenyl-8-(thiophene-2-carbonyl)-furo[2,3-h]chromen-2-one (8g, IC50 = 70 nM) showed 64-fold enhanced activity compared to the high throughput screening (HTS) hit 6a. Also, 8g was found effective in case of influenza A (H3N2) and influenza B virus strains similar to approved anti-influenza drug zanamivir (4). Preliminary mechanistic studies suggest that these compounds act as anti-influenza agents by inhibiting ribonucleoprotein (RNP) complex associated activity and have the potential to be developed further, Which Could form the basis for developing additional defense against influenza pandemics.

  DOI：

  10.1021/jm901570x
• 作为产物：
  描述：

  8-Benzoyl-7-hydroxy-4-methylcoumarin 、 二甲氨基硫代甲酰氯 在 4-二甲氨基吡啶 、 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 24.0h， 以84%的产率得到dimethylthiocarbamic acid O-(8-benzoyl-4-methyl-2-oxo-2H-chromen-7-yl) ester
  参考文献：
  名称：

  Anti-Influenza Drug Discovery: Structure−Activity Relationship and Mechanistic Insight into Novel Angelicin Derivatives

  摘要：

  By using a cell-based high throughput screening campaign,a novel angelicin derivative 6a was identified to inhibit influenza A (H1N1) virus induced Cytopathic effect in Madin-Darby canine kidney cell culture in low micromolar range. Detailed structure-activity relationship studies of 6a revealed that the angelicin scaffold is essential for activity in pharmacophore B, while meta-substituted phenyl/2-thiophene rings are optimal ill pharmacophore A and C. The optimized lead 4-methyl-9-phenyl-8-(thiophene-2-carbonyl)-furo[2,3-h]chromen-2-one (8g, IC50 = 70 nM) showed 64-fold enhanced activity compared to the high throughput screening (HTS) hit 6a. Also, 8g was found effective in case of influenza A (H3N2) and influenza B virus strains similar to approved anti-influenza drug zanamivir (4). Preliminary mechanistic studies suggest that these compounds act as anti-influenza agents by inhibiting ribonucleoprotein (RNP) complex associated activity and have the potential to be developed further, Which Could form the basis for developing additional defense against influenza pandemics.

  DOI：

  10.1021/jm901570x

文献信息

• Anti-Influenza Drug Discovery: Structure−Activity Relationship and Mechanistic Insight into Novel Angelicin Derivatives
  作者：Jiann-Yih Yeh、Mohane Selvaraj Coumar、Jim-Tong Horng、Hui-Yi Shiao、Fu-Ming Kuo、Hui-Ling Lee、In-Chun Chen、Chun-Wei Chang、Wen-Fang Tang、Sung-Nain Tseng、Chi-Jene Chen、Shin-Ru Shih、John T.-A. Hsu、Chun-Chen Liao、Yu-Sheng Chao、Hsing-Pang Hsieh

  DOI：10.1021/jm901570x

  日期：2010.2.25

  By using a cell-based high throughput screening campaign,a novel angelicin derivative 6a was identified to inhibit influenza A (H1N1) virus induced Cytopathic effect in Madin-Darby canine kidney cell culture in low micromolar range. Detailed structure-activity relationship studies of 6a revealed that the angelicin scaffold is essential for activity in pharmacophore B, while meta-substituted phenyl/2-thiophene rings are optimal ill pharmacophore A and C. The optimized lead 4-methyl-9-phenyl-8-(thiophene-2-carbonyl)-furo[2,3-h]chromen-2-one (8g, IC50 = 70 nM) showed 64-fold enhanced activity compared to the high throughput screening (HTS) hit 6a. Also, 8g was found effective in case of influenza A (H3N2) and influenza B virus strains similar to approved anti-influenza drug zanamivir (4). Preliminary mechanistic studies suggest that these compounds act as anti-influenza agents by inhibiting ribonucleoprotein (RNP) complex associated activity and have the potential to be developed further, Which Could form the basis for developing additional defense against influenza pandemics.