4-(4-aminophenylthio)-N-benzylpicolinamide | 1061639-82-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-(4-aminophenylthio)-N-benzylpicolinamide
• 英文别名: 4-(4-aminophenyl)sulfanyl-N-benzylpyridine-2-carboxamide
• CAS: 1061639-82-4
• 化学式: C₁₉H₁₇N₃OS
• 分子量: 335.429
• InChiKey: KGVBUGRTIASFDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-aminophenylthio)-N-benzylpicolinamide 、 苯甲酰异氰酸脂 以 1,4-二氧六环 为溶剂， 生成 4-[4-(benzoylcarbamoylamino)phenyl]sulfanyl-N-benzylpyridine-2-carboxamide
  参考文献：
  名称：

  Novel Microtubule-Interacting Phenoxy Pyridine and Phenyl Sulfanyl Pyridine Analogues for Cancer Therapy

  摘要：

  Current microtubule inhibitory agents used in the clinic to treat cancer have severe side effects, and development of resistance is frequent. We have evaluated the antitumor effect of a novel 30-compound library of phenoxy pyridine and phenyl sulfanyl pyridine derivatives. MTT assays revealed that, of all 30 compounds tested, compounds 2 and 3 showed the largest decrease in proliferation (low mu M range) against Panel and HS766T human pancreatic cancer cells. Flow cytometry experiments with MCF7 breast cancer cells showed a G2/M arrest comparable to that of colcemid. Immunofluorescence staining demonstrated complete disappearance of intracellular microtubules. Tubulin assembly assays, however, showed a dose-dependent decrease in tubulin assembly with compound 3 that seemed limited to about 50% of the control reaction. With compound 2 treatment, there was only a delay in the onset of assembly, with no effect on the extent of the reaction. Taken together, our results show that these novel microtubule inhibitors have promising anticancer activity and can be potentially used to overcome paclitaxel resistance in the clinical setting.

  DOI：

  10.1021/jm800203e
• 作为产物：
  描述：

  4-氯吡啶-2-甲酸甲酯 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 4-(4-aminophenylthio)-N-benzylpicolinamide
  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

• 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.
• Novel Microtubule-Interacting Phenoxy Pyridine and Phenyl Sulfanyl Pyridine Analogues for Cancer Therapy
  作者：Ravi Kumar Anchoori、Madeleine Susanne Quirine Kortenhorst、Manuel Hidalgo、Taradas Sarkar、Gurulingappa Hallur、Ruoli Bai、Paul J. Van Diest、Ernest Hamel、Saeed R. Khan

  DOI：10.1021/jm800203e

  日期：2008.10.9

  Current microtubule inhibitory agents used in the clinic to treat cancer have severe side effects, and development of resistance is frequent. We have evaluated the antitumor effect of a novel 30-compound library of phenoxy pyridine and phenyl sulfanyl pyridine derivatives. MTT assays revealed that, of all 30 compounds tested, compounds 2 and 3 showed the largest decrease in proliferation (low mu M range) against Panel and HS766T human pancreatic cancer cells. Flow cytometry experiments with MCF7 breast cancer cells showed a G2/M arrest comparable to that of colcemid. Immunofluorescence staining demonstrated complete disappearance of intracellular microtubules. Tubulin assembly assays, however, showed a dose-dependent decrease in tubulin assembly with compound 3 that seemed limited to about 50% of the control reaction. With compound 2 treatment, there was only a delay in the onset of assembly, with no effect on the extent of the reaction. Taken together, our results show that these novel microtubule inhibitors have promising anticancer activity and can be potentially used to overcome paclitaxel resistance in the clinical setting.