1-[(4-chlorophenyl)methyl]-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide | 255911-25-2

• 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: 1-[(4-chlorophenyl)methyl]-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide
• 英文别名: 1-[(4-Chlorophenyl)methyl]-2,2-dioxo-2lambda6,1,3-benzothiadiazin-4-one；1-[(4-chlorophenyl)methyl]-2,2-dioxo-2λ6,1,3-benzothiadiazin-4-one
• CAS: 255911-25-2
• 化学式: C₁₄H₁₁ClN₂O₃S
• 分子量: 322.772
• InChiKey: CLPIWODOQQJNGE-UHFFFAOYSA-N

物化性质

• 熔点：
  285-287 °C
• 密度：
  1.489±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[(4-chlorophenyl)methyl]-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide 在 硫酸氢铵 、 三氟化硼乙醚 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 1-[(4-chlorophenyl)methyl]-3-(benzyloxymethyl)-2,1,3-benzothiadiazin-4-one 2,2-dioxide
  参考文献：
  名称：

  非核苷人巨细胞病毒抑制剂：(氯苯基甲基）苯并噻二嗪二氧化物衍生物的合成和抗病毒评估。

  摘要：

  主要利用苄基化反应合成了第二代苯并噻二嗪二氧化物（BTD）衍生物。氯苯基甲基BTD衍生物具有抗人巨细胞病毒（HCMV）的活性，IC（50）值为3至10 microM。它们对肺成纤维细胞HEL细胞增殖的50％细胞毒性浓度通常> 200 microM，而淋巴细胞CME细胞的生长浓度在20至35 microM之间。考虑细胞形态的细胞毒性时，不同BTD衍生物的最小细胞毒性浓度在5到200 microM之间变化。一些抗HCMV化合物还显示出抗HIV-1和HIV-2的活性。氯苯基甲基衍生物21对多种来自具有不同临床表现的患者的HCMV临床分离株具有活性，并完全保持了其对更昔洛韦耐药的HCMV株的活性。二苄基BTD衍生物不抑制HCMV蛋白酶，初步的药理实验表明，它们的抗HCMV作用源于对病毒复制周期早期的干扰。

  DOI：

  10.1021/jm000118q
• 作为产物：
  描述：

  4-氯氯苄 、 4-hydroxy-2,1,3-benzothiadiazine 2,2-dioxide 在 碳酸氢钠 作用下， 反应 2.0h， 以63%的产率得到1-[(4-chlorophenyl)methyl]-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide
  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

• Chlorophenylmethyl benzothiadiazine dioxides derivatives: Potent human cytomegalovirus inhibitors
  作者：Ana Martinez、Carmen Gil、Concepción Perez、Ana Castro、Columbiana Prieto、Joaquín Otero

  DOI：10.1016/s0960-894x(99)00538-7

  日期：1999.11

  lead compounds, acyclonucleosides derived from 2,1,3-benzothiadiazine dioxides, in the search for inhibitors of human cytomegalovirus (HCMV), lead us to identify the chlorophenylmethyl benzothiadiazine dioxides derivatives as potent HCMV inhibitors. The synthesis and antiviral data of this second-generation of benzothiadiazine dioxide compounds are reported.

  在寻找人类巨细胞病毒（HCMV）抑制剂时，我们先前报道的先导化合物，即衍生自2,1,3-苯并噻二嗪二氧化物的无环核苷的修饰，使我们确定了氯苯基甲基苯并噻二嗪二氧化物衍生物是有效的HCMV抑制剂。报道了该第二代苯并噻二嗪二氧化物化合物的合成和抗病毒数据。
• Benzothiadiazine dioxides (BTD) derivatives as non-nucleoside human cytomegalovirus (HCMV) inhibitors. study of structural requirements for biological activity☆
  作者：Ana Martinez、Carmen Gil、Ana Castro、Concepción Pérez、Columbiana Prieto、Joaquin Otero

  DOI：10.1016/s0968-0896(03)00148-2

  日期：2003.5.29

  Two new series of BTD derivatives have been synthesised allowing to explore the steric requirements for their biological activity. The N3-alkylBTD compounds have shown antiviral activity in the same order or lower than previously prepared compounds. However, the cytotoxicity values observed prevent this new series of BTD derivatives from its potential therapeutic application. Concerning BTD derivatives with the modified linker attached to N1 position, we have obtained new non-nucleoside anti-HCMV derivatives. The activity against HCMV is shown at concentrations that were 10-fold lower than the concentration that was toxic for the host cells, which confirm that these derivatives show a specific antiviral effect against HCMV. SAR conclusions derived from these last compounds have provided new knowledge about the structural requirements of BTD showing certain positions that could be modified for enhancing the anti-HCMV action. (C) 2003 Elsevier Science Ltd. All rights reserved.
• 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.
• Nonnucleoside Human Cytomegalovirus Inhibitors:  Synthesis and Antiviral Evaluation of (Chlorophenylmethyl)benzothiadiazine Dioxide Derivatives
  作者：Ana Martinez、Carmen Gil、Concepción Perez、Ana Castro、Columbiana Prieto、Joaquín Otero、Graciela Andrei、Robert Snoeck、Jan Balzarini、Erik De Clercq

  DOI：10.1021/jm000118q

  日期：2000.8.1

  A second generation of benzothiadiazine dioxide (BTD) derivatives was synthesized employing benzylation reactions mainly. The chlorophenylmethyl BTD derivatives showed activity against human cytomegalovirus (HCMV) with IC(50) values ranging from 3 to 10 microM. Their 50% cytotoxic concentrations were often >200 microM to lung fibroblast HEL cell proliferation and between 20 and 35 microM for lymphocyte

  主要利用苄基化反应合成了第二代苯并噻二嗪二氧化物（BTD）衍生物。氯苯基甲基BTD衍生物具有抗人巨细胞病毒（HCMV）的活性，IC（50）值为3至10 microM。它们对肺成纤维细胞HEL细胞增殖的50％细胞毒性浓度通常> 200 microM，而淋巴细胞CME细胞的生长浓度在20至35 microM之间。考虑细胞形态的细胞毒性时，不同BTD衍生物的最小细胞毒性浓度在5到200 microM之间变化。一些抗HCMV化合物还显示出抗HIV-1和HIV-2的活性。氯苯基甲基衍生物21对多种来自具有不同临床表现的患者的HCMV临床分离株具有活性，并完全保持了其对更昔洛韦耐药的HCMV株的活性。二苄基BTD衍生物不抑制HCMV蛋白酶，初步的药理实验表明，它们的抗HCMV作用源于对病毒复制周期早期的干扰。