4-[(4-aminophenylthio)(2-pyridyl)]-N-methylcarboxamide | 284462-87-9

• 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)(2-pyridyl)]-N-methylcarboxamide
• 英文别名: 4-(4-aminophenylthio)-N-methylpicolinamide；4-((4-aminophenyl)thio)-N-methylpyridine-2-carboxamide；4-(4-amino-phenylsulfanyl)-pyridine-2-carboxylic acid methylamide；4-(4-aminophenyl)sulfanyl-N-methylpyridine-2-carboxamide
• CAS: 284462-87-9
• 化学式: C₁₃H₁₃N₃OS
• mdl: MFCD13459229
• 分子量: 259.332
• InChiKey: QQGAKTGEJKOMRI-UHFFFAOYSA-N

物化性质

• 沸点：
  532.7±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.076
• 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)(2-pyridyl)]-N-methylcarboxamide 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.33h， 生成 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)(2-pyridyl)]-N-methylcarboxamide
  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

• Phenolics and Flavonoids Compounds, Phenylanine Ammonia Lyase and Antioxidant Activity Responses to Elevated CO2 in Labisia pumila (Myrisinaceae)
  作者：Hawa Z.E. Jaafar、Mohd Hafiz Ibrahim、Ehsan Karimi

  DOI：10.3390/molecules17066331

  日期：——

  A split plot 3 × 3 experiment was designed to examine the impact of three concentrations of CO2 (400, 800 and 1,200 µmol·mol−1) on the phenolic and flavonoid compound profiles, phenylalanine ammonia lyase (PAL) and antioxidant activity in three varieties of Labisia pumila Benth. (var. alata, pumila and lanceolata) after 15 weeks of exposure. HPLC analysis revealed a strong influence of increased CO2 concentration on the modification of phenolic and flavonoid profiles, whose intensity depended on the interaction between CO2 levels and L. pumila varieties. Gallic acid and quercetin were the most abundant phenolics and flavonoids commonly present in all the varieties. With elevated CO2 (1,200 µmol·mol−1) exposure, gallic acid increased tremendously, especially in var. alata and pumila (101–111%), whilst a large quercetin increase was noted in var. lanceolata (260%), followed closely by alata (201%). Kaempferol, although detected under ambient CO2 conditions, was undetected in all varieties after exposure. Instead, caffeic acid was enhanced tremendously in var. alata (338~1,100%) and pumila (298~433%). Meanwhile, pyragallol and rutin were only seen in var. alata (810 µg·g−1 DW) and pumila (25 µg·g−1 DW), respectively, under ambient conditions; but the former compound went undetected in all varieties while rutin continued to increase by 262% after CO2 enrichment. Interestingly, naringenin that was present in all varieties under ambient conditions went undetected under enrichment, except for var. pumila where it was enhanced by 1,100%. PAL activity, DPPH and FRAP also increased with increasing CO2 levels implying the possible improvement of health-promoting quality of Malaysian L. pumila under high CO2 enrichment conditions.

  设计了一个裂区 3 × 3 实验，以研究三种 CO2 浓度（400、800 和 1,200 µmol·mol−1）对三种Labisia pumila Benth品种（var. alata、pumila 和 lanceolata）在 15周暴露后的酚类和黄酮类化合物谱、苯丙氨酸解氨酶（PAL）和抗氧化活性的影响。HPLC分析揭示了增加的 CO2 浓度对酚类和黄酮类化合物谱修改的强烈影响，其强度取决于 CO2 水平和 L. pumila 品种之间的相互作用。没食子酸和槲皮素是所有品种中最丰富的常见酚类和黄酮类化合物。在升高 CO2（1,200 µmol·mol−1）暴露下，没食子酸显著增加，特别是在 var. alata 和 pumila 中增加了 101-111%，而在 var. lanceolata 中槲皮素大幅增加 260%，其次是 alata 增加 201%。虽然在新风条件下检测到山奈酚，但在所有品种暴露后均未检测到。相反，咖啡酸在 var. alata（338-1,100%）和 pumila（298-433%）中大大增强。同时，pyragallol 和rutin仅在新风条件下出现在 var. alata（810 µg·g−1 DW）和 pumila（25 µg·g−1 DW）中，但前一种化合物在所有品种中均未检测到，而rutin在 CO2 富集后继续增加 262%。有趣的是，在新风条件下所有品种中存在的柚皮素在富集条件下均未检测到，除了 var. pumila 中增强了 1,100%。随着 CO2 水平的增加，PAL 活性、DPPH 和 FRAP 也增加，这意味着马来西亚 L. pumila 在高 CO2 富集条件下可能改善其促进健康的品质。
• UREA COMPOUNDS USEFUL IN THE TREATMENT OF CANCER
  申请人：Smith Roger

  公开号：US20110195110A1

  公开（公告）日：2011-08-11

  Pyrazole urea compounds, pharmaceutical compositions which contain them and methods for treating cancer using them.

  吡唑脲类化合物，含有它们的制药组合物以及使用它们治疗癌症的方法。
• AURORA KINASE MODULATORS AND METHODS OF USE
  申请人：Deak Holly L.

  公开号：US20110301162A1

  公开（公告）日：2011-12-08

  The present invention relates to chemical compounds having a general formula I wherein A 1-6 , L 1 , R 1 , R 4-6 and n are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinase proteins. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds and methods of treating disease states related to the activity of Aurora kinase.

  本发明涉及具有一般式I的化合物，其中A1-6、L1、R1、R4-6和n如此定义，并且能够调节各种蛋白激酶受体酶，从而影响与这些激酶蛋白的活动相关的各种疾病状态和条件。例如，这些化合物能够调节极光激酶，从而影响细胞周期和细胞增殖的过程，以治疗癌症和癌症相关疾病。本发明还包括制药组合物，包括这些化合物以及治疗与极光激酶活性相关的疾病状态的方法。
• CSF-1R, Inhibitors, Compositions, and Methods of Use
  申请人：Sutton James

  公开号：US20100261679A1

  公开（公告）日：2010-10-14

  Disclosed herein are compounds and their oxides, esters, prodrugs, solvates, and pharmaceutically acceptable salts thereof, compositions of the compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier, and uses of the compounds, either alone or in combination with at least one additional therapeutic agent. The embodiments are useful for inhibiting cellular proliferation, inhibiting the growth and/or metathesis of tumors, treating or preventing cancer, treating or preventing degenerating bone diseases such as rheumatoid arthritis, and/or inhibiting molecules such as CSF-1R.

  本文公开了化合物及其氧化物、酯、前药、溶剂化物和其药学上可接受的盐，以及化合物的组合物，可以单独使用或与至少一种其他治疗剂合用，并与药学上可接受的载体一起使用，以及化合物的用途，可以单独使用或与至少一种其他治疗剂合用。这些实施例可用于抑制细胞增殖，抑制肿瘤的生长和/或代谢，治疗或预防癌症，治疗或预防类风湿性关节炎等骨骼退化性疾病，并/或抑制分子如CSF-1R。
• 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.