4-(2-Biphenyl-4-yl-2-oxo-ethyl)-3,3-dioxo-3,4-dihydro-2H-3lambda*6*,9-dithia-2,4-diaza-fluoren-1-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(2-Biphenyl-4-yl-2-oxo-ethyl)-3,3-dioxo-3,4-dihydro-2H-3lambda*6*,9-dithia-2,4-diaza-fluoren-1-one
• 英文别名: 2,2-dioxo-1-[2-oxo-2-(4-phenylphenyl)ethyl]-[1]benzothiolo[3,2-c][1,2,6]thiadiazin-4-one
• 化学式: C₂₃H₁₆N₂O₄S₂
• 分子量: 448.523
• InChiKey: WBSCQMWXDKVNIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-氨基苯并[b]噻吩-2-羧酸甲酯 在 sodium hydroxide 、 氨基磺酰氯 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 56.0h， 生成 4-(2-Biphenyl-4-yl-2-oxo-ethyl)-3,3-dioxo-3,4-dihydro-2H-3lambda*6*,9-dithia-2,4-diaza-fluoren-1-one
  参考文献：
  名称：

  Benzyl Derivatives of 2,1,3-Benzo- and Benzothieno[3,2-a]thiadiazine 2,2-Dioxides:  First Phosphodiesterase 7 Inhibitors

  摘要：

  The synthesis of a new family of benzyl derivatives of 2,1,3-benzo- and benzothieno[3,2-a]-thiadiazine 2,2-dioxides was achieved. The biological data revealed the first heterocyclic family of compounds with PDE 7 inhibitory properties appearing to be a new objective for the treatment of T-cell-dependent disorders. The IC50 values or percent inhibition values of the compounds against PDE 7 were calculated by testing them against human recombinant PDE 7 expressed in S, cerevisiae. In this expression system the only cyclic nucleotide hydrolyzing activity present in cell extracts corresponded to human PDE 7. Isoenzyme selectivity PDE 7 versus PDE 4 and PDE 3 was also measured. Considering simultaneously inhibition of the three different isoenzymes, monobenzyl derivatives 15 and 23 showed interesting PDE 7 potency (around 10 mu M); although not statistically significant, a trend toward selectivity with respect to PDE 3 and PDE 4 was obtained. Benzothiadiazine 16, although less potent at PDE 7 (IC50 25 mu M), also showed a trend of selectivity toward PDE 3 and PDE 4. These compounds are considered the best leads for further optimization.

  DOI：

  10.1021/jm990382n

文献信息

• Benzyl Derivatives of 2,1,3-Benzo- and Benzothieno[3,2-<i>a</i>]thiadiazine 2,2-Dioxides:  First Phosphodiesterase 7 Inhibitors
  作者：Ana Martínez、Ana Castro、Carmen Gil、Montserrat Miralpeix、Victor Segarra、Teresa Doménech、Jorge Beleta、Jose M. Palacios、Hamish Ryder、Xavier Miró、Carles Bonet、Josep M. Casacuberta、Ferran Azorín、Benjamí Piña、Pere Puigdoménech

  DOI：10.1021/jm990382n

  日期：2000.2.1

  The synthesis of a new family of benzyl derivatives of 2,1,3-benzo- and benzothieno[3,2-a]-thiadiazine 2,2-dioxides was achieved. The biological data revealed the first heterocyclic family of compounds with PDE 7 inhibitory properties appearing to be a new objective for the treatment of T-cell-dependent disorders. The IC50 values or percent inhibition values of the compounds against PDE 7 were calculated by testing them against human recombinant PDE 7 expressed in S, cerevisiae. In this expression system the only cyclic nucleotide hydrolyzing activity present in cell extracts corresponded to human PDE 7. Isoenzyme selectivity PDE 7 versus PDE 4 and PDE 3 was also measured. Considering simultaneously inhibition of the three different isoenzymes, monobenzyl derivatives 15 and 23 showed interesting PDE 7 potency (around 10 mu M); although not statistically significant, a trend toward selectivity with respect to PDE 3 and PDE 4 was obtained. Benzothiadiazine 16, although less potent at PDE 7 (IC50 25 mu M), also showed a trend of selectivity toward PDE 3 and PDE 4. These compounds are considered the best leads for further optimization.