2,2-dioxo-1H-[1]benzothiolo[3,2-c][1,2,6]thiadiazin-4-one | 250281-27-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 2,2-dioxo-1H-[1]benzothiolo[3,2-c][1,2,6]thiadiazin-4-one
• CAS: 250281-27-7
• 化学式: C₉H₆N₂O₃S₂
• 分子量: 254.29
• InChiKey: YKFZDCONGNJLFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,2-dioxo-1H-[1]benzothiolo[3,2-c][1,2,6]thiadiazin-4-one 、 3,4-二氯氯苄 在 碳酸氢钠 作用下， 以 水 为溶剂， 反应 3.0h， 生成 1-[(3,4-dichlorophenyl)methyl]-1H-benzo[4,5]thieno[3,2-c]-1,2,6-thiadiazin-4(3H)-one 2,2-dioxide
  参考文献：
  名称：

  CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application example

  摘要：

  Phosphodiesterase (PDE) 7 is a high affinity cAMP-specific PDE whose functional role in T-cells has been the subject of some controversy. Recent findings on tissue distribution, however, support the hypothesis that PDE7 could be a good target for the treatment of airway diseases, T-cell related diseases or central nervous system (CNS) disorders. Therefore, the identification of selective inhibitors targeted against PDE7 enzyme has become an attractive area of research. We report here the first use of the descriptors generated by the CODES program for ligand-based virtual screening. This program codifies molecules from a topological point of view and the generated descriptors are related to the chemical nature of the atoms, the atomic bonds and the connectivity with the rest of the molecule. They are also able to distinguish among stereoisomers. By using this approach, 173 compounds were codified, and their similarity with the reference compound was analysed. Based on the analysis, new potential PDE7 inhibitors have been identified, synthesized and biologically evaluated confirming that CODES descriptors are valid for ligand-based virtual screening and provided new lead compounds for further optimization as potent and selective PDE7 inhibitors. (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.10.027
• 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 作用下， 以 甲苯 为溶剂， 反应 8.0h， 生成 2,2-dioxo-1H-[1]benzothiolo[3,2-c][1,2,6]thiadiazin-4-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.
• CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application example
  作者：Ana Castro、María José Jerez、Carmen Gil、Félix Calderón、Teresa Doménech、Arsenio Nueda、Ana Martínez

  DOI：10.1016/j.ejmech.2007.10.027

  日期：2008.7

  Phosphodiesterase (PDE) 7 is a high affinity cAMP-specific PDE whose functional role in T-cells has been the subject of some controversy. Recent findings on tissue distribution, however, support the hypothesis that PDE7 could be a good target for the treatment of airway diseases, T-cell related diseases or central nervous system (CNS) disorders. Therefore, the identification of selective inhibitors targeted against PDE7 enzyme has become an attractive area of research. We report here the first use of the descriptors generated by the CODES program for ligand-based virtual screening. This program codifies molecules from a topological point of view and the generated descriptors are related to the chemical nature of the atoms, the atomic bonds and the connectivity with the rest of the molecule. They are also able to distinguish among stereoisomers. By using this approach, 173 compounds were codified, and their similarity with the reference compound was analysed. Based on the analysis, new potential PDE7 inhibitors have been identified, synthesized and biologically evaluated confirming that CODES descriptors are valid for ligand-based virtual screening and provided new lead compounds for further optimization as potent and selective PDE7 inhibitors. (c) 2007 Elsevier Masson SAS. All rights reserved.