N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methylformamide)(4-pyridylthio)phenyl]thiourea | 1246391-76-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methylformamide)(4-pyridylthio)phenyl]thiourea
• 英文别名: 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)thioureido)phenylthio)-N-methylpicolinamide；4-((4-(3-(4-chloro-3-(trifluoromethyl)phenyl)thioureido)phenyl)thio)-N-methylpicolinamide；4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamothioylamino]phenyl]sulfanyl-N-methylpyridine-2-carboxamide
• CAS: 1246391-76-3
• 化学式: C₂₁H₁₆ClF₃N₄OS₂
• 分子量: 496.964
• InChiKey: LIRQPNOKNKKMQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methylformamide)(4-pyridylthio)phenyl]thiourea 、 对甲苯磺酸 以 乙醇 为溶剂， 反应 1.33h， 以77.6%的产率得到N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methylformamide)(4-pyridylthio)phenyl]thiourea toluenesulfonate
  参考文献：
  名称：

  ANTICANCER COMPOUNDS AND PREPARATION METHODS THEREOF

  摘要：

  两种新化合物具有抗癌作用，分别为N-[4-氯-3-(三氟甲基)苯基]-[4-(N-甲基-甲酰胺)(4-吡啶氧基)苯基]-硫脲和N-[4-氯-3-(三氟甲基)苯基]-[4-(N-甲基-甲酰胺)(4-吡啶硫基)苯基]-硫脲，以及它们的盐。进一步披露了这两种新化合物的制备方法和含有这些新化合物的药物组合物。实验研究表明，这两种新化合物可以有效抑制Raf和VEGFR蛋白激酶的活性，广泛抑制各种类型的人类肿瘤细胞系的生长，并进一步诱导肿瘤细胞凋亡。人类肿瘤异种移植模型研究证明，这两种新化合物是有效的抗肿瘤药物，可以显著抑制体内人类肝癌细胞、肺癌细胞和肠癌细胞的生长。此外，这些化合物的抗癌作用远远优于索拉非尼。

  公开号：

  US20130225641A1
• 作为产物：
  描述：

  (4-氯-3-(三氟甲基)苯基)氨基二硫代甲酸 在 三光气 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 生成 N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methylformamide)(4-pyridylthio)phenyl]thiourea
  参考文献：
  名称：

  Thiourea and thioether derivatives of sorafenib: synthesis, crystal structure, and antiproliferative activity

  摘要：

  A series of novel sorafenib derivatives containing diaryl thiourea and thioether, 9a-u, was designed and synthesized, and their antiproliferative activities against HCT116 and MDA-MB-231 cell lines were also evaluated and described. Most compounds exhibited potent antiproliferative activity against HCT116 cells with IC50 = 1.8-80.4 mu M. Compounds 9p, 9r, and 9s demonstrated competitive antiproliferative activities to sorafenib, against all two cancer cell lines. The structures of all the newly synthesized compounds were determined by H-1 NMR, C-13 NMR, and HRMS, and compound 9n was characterized by single-crystal X-ray diffraction. Primary structure-activity relationships (SAR) have also been established.

  DOI：

  10.1007/s00044-012-0400-8

文献信息

• ANTICANCER COMPOUNDS AND PREPARATION METHODS THEREOF
  申请人：Co., Ltd. Banghe Pharmaceutical

  公开号：US20130225641A1

  公开（公告）日：2013-08-29

  Two new compounds with anticancer effects of N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methyl-formamide)(4-pyridyloxy)phenyl]-thiourea and N-[4-chloro-3-(trifluoromethyl)phenyl]-[4-(N-methyl-formamide)(4-pyridylthio)phenyl]-thiourea, and salts thereof are disclosed. Preparation methods of the two new compounds and pharmaceutical compositions containing the new compounds are further disclosed. Experimental studies show that the two new compounds can effectively inhibit the activity of Raf and VEGFR protein kinase, widely inhibit growth of various types of human tumor cell lines and further induce apoptosis of tumor cells. Human tumor heterograft model investigation proves that the two new compounds are effective antineoplastic agents, and can sharply inhibit growth of human liver cancer cells, lung cancer cells and intestinal cancer cells in vivo. Furthermore, the anticancer effects of the compounds are much better than that of Sorafenib.

  两种新化合物具有抗癌作用，分别为N-[4-氯-3-(三氟甲基)苯基]-[4-(N-甲基-甲酰胺)(4-吡啶氧基)苯基]-硫脲和N-[4-氯-3-(三氟甲基)苯基]-[4-(N-甲基-甲酰胺)(4-吡啶硫基)苯基]-硫脲，以及它们的盐。进一步披露了这两种新化合物的制备方法和含有这些新化合物的药物组合物。实验研究表明，这两种新化合物可以有效抑制Raf和VEGFR蛋白激酶的活性，广泛抑制各种类型的人类肿瘤细胞系的生长，并进一步诱导肿瘤细胞凋亡。人类肿瘤异种移植模型研究证明，这两种新化合物是有效的抗肿瘤药物，可以显著抑制体内人类肝癌细胞、肺癌细胞和肠癌细胞的生长。此外，这些化合物的抗癌作用远远优于索拉非尼。
• Thiourea and thioether derivatives of sorafenib: synthesis, crystal structure, and antiproliferative activity
  作者：Jianwen Yao、Jing Chen、Zuopeng He、Wei Sun、Hao Fang、Wenfang Xu

  DOI：10.1007/s00044-012-0400-8

  日期：2013.8

  A series of novel sorafenib derivatives containing diaryl thiourea and thioether, 9a-u, was designed and synthesized, and their antiproliferative activities against HCT116 and MDA-MB-231 cell lines were also evaluated and described. Most compounds exhibited potent antiproliferative activity against HCT116 cells with IC50 = 1.8-80.4 mu M. Compounds 9p, 9r, and 9s demonstrated competitive antiproliferative activities to sorafenib, against all two cancer cell lines. The structures of all the newly synthesized compounds were determined by H-1 NMR, C-13 NMR, and HRMS, and compound 9n was characterized by single-crystal X-ray diffraction. Primary structure-activity relationships (SAR) have also been established.