Background: A novel series of pyridine containing 1,3,4-oxa/thiadiazol derivatives 4a,b, pyrazole derivatives 5-7, thiazole derivatives 9a,b and 17a-c, urea derivatives 12a-c, imidiazole derivative 16, imidazo[1,2-a]pyridine derivatives 18a, b, tetrazole 19, pyrane 20 and pyridine derivatives 21 has been synthesized.

Objective: This research aims to synthesize 6-(Trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl] amino} nicotinohydrazide 2 and 6-(trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl]amino} pyridin-3-carboaldhyde 15 as key intermediate for the synthesis of novel pyridine derivatives bearing different heterocyclic rings in order to study the additive effect of this ring toward tumor cell lines.

Methods: 6-(Trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl]amino} nicotinohydrazide 2 was synthesized in a series of synthetic steps and was used as key intermediate for the synthesis of compounds 3-(1,3,4- oxa/thiadiazol-2-yl)-6-(trifluoromethyl)-N-(3- trifluoromethyl) phenyl) pyridin-2-amine 4a,b, (3,5-dimethyl- 1H-pyrazol-1-yl derivatives) [6-(trifluoromethyl)-2-{[3- trifluoromethyl) phenyl] amino} pyridin-3- yl]methanone 5a,b, 6-8, 9a,b and 12a-c. Also, 6-(trifluoromethyl)-2-{[3-(trifluoromethyl)phenyl]amino} pyridin-3-carboaldhyde (15) was used as a key intermediate for the synthesis of novel series of pyridine derivatives with different heterocyclic ring (16-21).

Results: Structures of the newly synthesized compounds were established by elemental analysis and spectral data. All the synthesized compounds were screened for their in vitro anticancer activity against liver cancer (HepG2), human colon cancer (HT-29) and human breast adenocarcinoma cell lines (MCF-7).

Conclusion: All the synthesized compounds were investigated for their in vitro antitumor activity. Compounds 4b, 9a,b and 19 showed higher antitumor activity than the doxorubicin. Interestingly, pyridine with pfluorophenyl urea 12a demonstrated the most potent antitumor activity. The activity of these compounds is strongly dependent on the basic skeleton of the molecules and the nature of the heterocyclic ring attached to the pyridine moiety.

背景：一系列新型吡啶，其中包含1,3,4-氧杂/噻二唑衍生物4a，b，吡唑衍生物5-7，噻唑衍生物9a，b和17a-c，尿素衍生物12a-c，咪唑衍生物16，咪唑[已经合成了1，2-a]吡啶衍生物18a，b，四唑19，吡喃20和吡啶衍生物21。

目的：本研究旨在合成6-（三氟甲基）-2-{[3-（三氟甲基）苯基]氨基}烟酰肼2和6-（三氟甲基）-2-{[3-（三氟甲基）苯基]氨基}吡啶- 3-carboaldhyde 15作为合成带有不同杂环的新型吡啶衍生物的关键中间体，以研究该环对肿瘤细胞系的加和作用。

方法：通过一系列合成步骤合成了6-（三氟甲基）-2-{[3-（三氟甲基）苯基]氨基}烟酰肼2，并用作合成化合物3-（1,3,4的关键中间体） -氧杂/噻二唑-2-基）-6-（三氟甲基）-N-（3-三氟甲基）苯基）吡啶-2-胺4a，b，（3,5-二甲基-1H-吡唑-1-基衍生物） [6-（三氟甲基）-2-{[[3-三氟甲基）苯基]氨基}吡啶-3-基]甲酮5a，b，6-8、9a，b和12a-c。同样，使用6-（三氟甲基）-2-{[3-（三氟甲基）苯基]氨基}吡啶-3-羰醛（15）作为关键中间体，用于合成具有不同杂环的新型吡啶衍生物系列（16 -21）。

结果：通过元素分析和光谱数据确定了新合成化合物的结构。筛选所有合成的化合物对肝癌（HepG2），人结肠癌（HT-29）和人乳腺腺癌细胞系（MCF-7）的体外抗癌活性。

结论：所有合成的化合物均具有体外抗肿瘤活性。化合物4b，9a，b和19显示出比阿霉素更高的抗肿瘤活性。有趣的是，吡啶与全氟苯基脲12a表现出最有效的抗肿瘤活性。这些化合物的活性在很大程度上取决于分子的基本骨架和与吡啶部分连接的杂环的性质。