Author(s): Olga I. Adaeva, Dmitry V. Demchuk, Roman A. Dolotov, Tatiana S. Kuptsova, Marina N. Semenova and Victor V. Semenov*
Page: [1613 - 1620] Pages: 8
* (Excluding Mailing and Handling)
The synthesis of a series of multifunctionalized 4,5-diarylpyridazines via inverse electron-demand Diels-Alder reaction between highly oxygenated diarylacetylenes and unsubstituted 1,2,4,5-tetrazine was developed using polyalkoxybenzenes isolated from industrial essential oils as starting material. The reaction proceeded smoothly to afford combretastatin A-4 analogues with pyridazine linker in consistently high yield. In a phenotypic sea urchin embryo assay, diarylpyridazine with 3,4,5-trimethoxyphenyl and 3-amino- 4-methoxyphenyl aryl rings was identified as a potent antimitotic microtubule-destabilizing compound.
Keywords: Inverse electron-demand Diels-Alder reaction, polyalkoxybenzenes, combretastatin A-4 analogues, antimitotic activity, microtubule, diarylpyridazines, tetrazine, phenotypic sea urchin embryo assay.
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