| Summary: | 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-(<i>p</i>-tolylcarbamoyl)pyrimidin-2-yl)nicotinate (<b>12m</b>) and ethyl 6-(5-((3,4-difluorophenyl)carbamoyl)pyrimidin-2-yl)nicotinate (<b>12q</b>) show the best activities with IC<sub>50</sub> 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 <b>12m</b> and <b>12q</b> effectively inhibited the expression of collagen, and the content of hydroxyproline in cell culture medium in vitro, indicating that compounds <b>12m</b> and <b>12q</b> might be developed the novel anti-fibrotic drugs.
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