6-chloro-3-methylthio-7-(3-phenyl-1,2,4-oxadiazol-5-yl)-1,1-dioxo-1,4,2-benzodithiazine | 1398564-49-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-chloro-3-methylthio-7-(3-phenyl-1,2,4-oxadiazol-5-yl)-1,1-dioxo-1,4,2-benzodithiazine
• 英文别名: 7-(3-phenyl-1,2,4-oxadiazol-5-yl)-6-chloro-3-methylthio-1,1-dioxo-1,4,2-benzodithiazine；6-Chloro-3-methylsulfanyl-7-(3-phenyl-1,2,4-oxadiazol-5-yl)-1lambda6,4,2-benzodithiazine 1,1-dioxide；6-chloro-3-methylsulfanyl-7-(3-phenyl-1,2,4-oxadiazol-5-yl)-1λ6,4,2-benzodithiazine 1,1-dioxide
• CAS: 1398564-49-2
• 化学式: C₁₆H₁₀ClN₃O₃S₃
• 分子量: 423.925
• InChiKey: DVNGJLOEQDXDHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  144
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-chloro-3-methylthio-7-(3-phenyl-1,2,4-oxadiazol-5-yl)-1,1-dioxo-1,4,2-benzodithiazine 在 ammonium hydroxide 、 盐酸羟胺 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 生成 2-[4-Chloro-5-(3-phenyl-1,2,4-oxadiazol-5-yl)-2-[(3,4,5-trimethoxyphenyl)methylsulfanyl]phenyl]sulfonyl-1-hydroxyguanidine
  参考文献：
  名称：

  1-(2-Mercaptobenzenesulfonyl)-3-hydroxyguanidines – Novel potent antiproliferatives, synthesis and in vitro biological activity

  摘要：

  Twenty four 1-[2-alkylthio-5-(azol-2 or 5-yl)-4-chlorobenzenesulfonyl]-3-hydroxyguanidines 6a-x have been synthesized in order to evaluate their biological activity. Compounds 6a, 6c, 6d, 6f, 6g, 6i-p, 6r-t, and 6v-x were tested for their in vitro anticancer activity at the US National Cancer Institute. The highest in vitro anticancer activity was found for compounds 6d, 6g and 6k with GI(50) average value in the range 1.62-1.86 mu M, and TGI mean values 3.72-4.47 mu M, whereas the remaining compounds showed broad spectrum of anticancer activity at low micromolar GI(50) level against all tested cancer cell lines. These results were subjected to CoMSIA analysis to establish quantitative structure activity relationships. The results evidence that potency of these compounds correlates mainly with hydrophobic and polar surface properties of substituents located both at 2 and 5 positions of 1-(4-chlorobenzenesulfonyl) moiety of investigated 3-hydroxyguanidine series. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.042
• 作为产物：
  描述：

  chlorek kwasu 6-chloro-3-metylotio-1,1-diokso-1,4,2-benzoditiazyno-7-karboksylowego 以 甲苯 为溶剂， 生成 6-chloro-3-methylthio-7-(3-phenyl-1,2,4-oxadiazol-5-yl)-1,1-dioxo-1,4,2-benzodithiazine
  参考文献：
  名称：

  Novel 3-Amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine Derivatives with Anticancer Activity: Synthesis and QSAR Study

  摘要：

  一系列新的 3-氨基-6-氯-7-(azol-2 或 5-yl)-1,1-二氧代-1,4,2-苯并二噻嗪衍生物 5a–j 已被合成并在体外评估美国国家癌症研究所的抗增殖活性。最活跃的化合物 5h 对卵巢癌 (OVCAR-3) 和乳腺癌 (MDA-MB-468) 表现出显着的细胞毒性作用（癌细胞死亡分别为 10% 和 47%），并对前列腺癌 (DU-145) 具有良好的选择性）、结肠（SW-620）和肾（TK-10）癌细胞系。为了更深入地了解新化合物 5a-j 的结构-活性关系，已经应用了 QSAR 研究。理论计算允许识别属于 RDF（分别在 MOLT-4 和 UO-31 QSAR 模型中的 RDF055p 和 RDF145m）和 3D-MorSE（MOLT-4 和 UO-31 QSAR 模型中的 Mor32m 和 Mor16e）描述符的分子描述符类。基于这些数据，获得了具有良好鲁棒性和预测能力的QSAR模型。

  DOI：

  10.3390/molecules201219821

文献信息

• 1-(2-Mercaptobenzenesulfonyl)-3-hydroxyguanidines – Novel potent antiproliferatives, synthesis and in vitro biological activity
  作者：Kamil Brożewicz、Jarosław Sławiński

  DOI：10.1016/j.ejmech.2012.07.042

  日期：2012.9

  Twenty four 1-[2-alkylthio-5-(azol-2 or 5-yl)-4-chlorobenzenesulfonyl]-3-hydroxyguanidines 6a-x have been synthesized in order to evaluate their biological activity. Compounds 6a, 6c, 6d, 6f, 6g, 6i-p, 6r-t, and 6v-x were tested for their in vitro anticancer activity at the US National Cancer Institute. The highest in vitro anticancer activity was found for compounds 6d, 6g and 6k with GI(50) average value in the range 1.62-1.86 mu M, and TGI mean values 3.72-4.47 mu M, whereas the remaining compounds showed broad spectrum of anticancer activity at low micromolar GI(50) level against all tested cancer cell lines. These results were subjected to CoMSIA analysis to establish quantitative structure activity relationships. The results evidence that potency of these compounds correlates mainly with hydrophobic and polar surface properties of substituents located both at 2 and 5 positions of 1-(4-chlorobenzenesulfonyl) moiety of investigated 3-hydroxyguanidine series. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Novel 3-Amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine Derivatives with Anticancer Activity: Synthesis and QSAR Study
  作者：Aneta Pogorzelska、Jarosław Sławiński、Kamil Brożewicz、Szymon Ulenberg、Tomasz Bączek

  DOI：10.3390/molecules201219821

  日期：——

  A series of new 3-amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine derivatives 5a–j have been synthesized and evaluated in vitro for their antiproliferative activity at the U.S. National Cancer Institute. The most active compound 5h showed significant cytotoxic effects against ovarian (OVCAR-3) and breast (MDA-MB-468) cancer (10% and 47% cancer cell death, respectively) as well as a good selectivity toward prostate (DU-145), colon (SW-620) and renal (TK-10) cancer cell lines. To obtain a deeper insight into the structure-activity relationships of the new compounds 5a–j QSAR studies have been applied. Theoretical calculations allowed the identification of molecular descriptors belonging to the RDF (RDF055p and RDF145m in the MOLT-4 and UO-31 QSAR models, respectively) and 3D-MorSE (Mor32m and Mor16e for MOLT-4 and UO-31 QSAR models) descriptor classes. Based on these data, QSAR models with good robustness and predictive ability have been obtained.

  一系列新的 3-氨基-6-氯-7-(azol-2 或 5-yl)-1,1-二氧代-1,4,2-苯并二噻嗪衍生物 5a–j 已被合成并在体外评估美国国家癌症研究所的抗增殖活性。最活跃的化合物 5h 对卵巢癌 (OVCAR-3) 和乳腺癌 (MDA-MB-468) 表现出显着的细胞毒性作用（癌细胞死亡分别为 10% 和 47%），并对前列腺癌 (DU-145) 具有良好的选择性）、结肠（SW-620）和肾（TK-10）癌细胞系。为了更深入地了解新化合物 5a-j 的结构-活性关系，已经应用了 QSAR 研究。理论计算允许识别属于 RDF（分别在 MOLT-4 和 UO-31 QSAR 模型中的 RDF055p 和 RDF145m）和 3D-MorSE（MOLT-4 和 UO-31 QSAR 模型中的 Mor32m 和 Mor16e）描述符的分子描述符类。基于这些数据，获得了具有良好鲁棒性和预测能力的QSAR模型。