Development, synthesis and biological evaluation of imidazole [2,1-b] thiazole derivatives containing an indole ring...

In this study, in order to further search anti-inflammatory drugs with high efficiency and low toxicity, this study took the ring of indoles and imidazole [2,1-b] thiazole as the main skeleton. A total of nine new N-1-substituted derivatives of indole-2-carboxyamide-phenylimidazoles [2,1-b] thiazole (13-20) was synthesized through the processes of cyclization, amino reduction, ester hydrolysis, dehydration condensation and acyl chloride substitution. These derivatives were then tested for their ability to reduce inflammation in RAW 264.7 macrophages. There was a significant majority of these compounds that effectively suppressed the production of NO, IL-6 and TNF-α in RAW 264.7 cells that were stimulated by LPS. One of these compounds, compound 19, was shown to be capable of efficiently lowering the levels of LPS-induced over expression of a number of inflammatory mediators. The inhibition rates for compound 19 were 54.66%, 68.82% and 43.74%, respectively. Additionally, an initial structure-activity relationship evaluation was carried out. The findings indicate that the incorporation of substituted benzyl moieties at the same position provided N-benzylation compounds with a positive anti-inflammatory effect. The electrophilicity of the substituent on the benzyl group had the potential to have an effect on the anti-inflammatory effect, which is something that calls for further investigation.