Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity.
Synthesis of Novel 2-(Pyridin-2-yl) Pyrimidine Derivatives and Study of Their Anti-Fibrosis Activity.
复制标题
新型2-(吡啶-2-基)嘧啶衍生物的合成及其抗纤维化活性研究
DOI：
10.3390/molecules25225226
复制
发表时间：
2020-11-10
期刊：
影响因子：
--
通讯作者：
Bai X
中科院分区：
文献类型：
--
作者：
Gu YF;Zhang Y;Yue FL;Li ST;Zhang ZQ;Li J;Bai X
嘧啶类化合物具有广泛的药理活性，已被用于药物化学中特殊结构的设计。为了制备具有潜在生物活性的新型杂环化合物库，设计合成了一系列新型2-（吡啶-2-基）嘧啶衍生物，并评价了其对永生化大鼠肝星状细胞（HSC-T6）的生物活性。其中14个化合物的抗肝纤维化活性优于吡非尼酮和Bipy 55 ′DC。其中化合物6-（5-（对甲苯基氨基甲酰基）嘧啶-2-基）烟酸乙酯（12 m）和6-（5-（（3，4-二氟苯基）氨基甲酰基）嘧啶-2-基）烟酸乙酯（12 q）表现出最好的活性，IC 50值分别为45.69 μM和45.81 μM。采用苦天狼星红染色、羟脯氨酸测定和ELISA检测Ⅰ型胶原α 1（Collagen type I alpha 1，COL 1A 1）蛋白表达，评价其抗肝纤维化活性。结果表明，化合物12 m和12 q在体外能有效抑制胶原蛋白的表达和细胞培养液中羟脯氨酸的含量，有望成为新型的抗肝纤维化药物。
A pyrimidine moiety exhibiting a wide range of pharmacological activities has been employed in the design of privileged structures in medicinal chemistry. To prepare libraries of novel heterocyclic compounds with potential biological activities, a series of novel 2-(pyridin-2-yl) pyrimidine derivatives were designed, synthesized and their biological activities were evaluated against immortalized rat hepatic stellate cells (HSC-T6). Fourteen compounds were found to present better anti-fibrotic activities than Pirfenidone and Bipy55′DC. Among them, compounds ethyl 6-(5-(p-tolylcarbamoyl)pyrimidin-2-yl)nicotinate (12m) and ethyl 6-(5-((3,4-difluorophenyl)carbamoyl)pyrimidin-2-yl)nicotinate (12q) show the best activities with IC50 values of 45.69 μM and 45.81 μM, respectively. Furthermore, the study of anti-fibrosis activity was evaluated by Picro-Sirius red staining, hydroxyproline assay and ELISA detection of Collagen type I alpha 1 (COL1A1) protein expression. Our study showed that compounds 12m and 12q effectively inhibited the expression of collagen, and the content of hydroxyproline in cell culture medium in vitro, indicating that compounds 12m and 12q might be developed the novel anti-fibrotic drugs.
登录
查看更多内容
影响因子：
15
作者：
Anderson ED;Boger DL
通讯作者：
Boger DL
影响因子：
4
作者：
Vasta JD;Andersen KA;Deck KM;Nizzi CP;Eisenstein RS;Raines RT
通讯作者：
Raines RT
影响因子：
4.2
作者：
Skerlj, Renato;Bridger, Gary;Schols, Dominique
通讯作者：
Schols, Dominique
影响因子：
3.5
作者：
Wagner, E;Becan, L;Nowakowska, E
通讯作者：
Nowakowska, E
影响因子：
3
作者：
Xiang, Jinbao;Leung, Crystal;Bai, Xu
通讯作者：
Bai, Xu