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Current Organic Chemistry

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ISSN (Online): 1875-5348

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Research Article

Synthesis of Polyoxygenated 4,5-Diarylpyridazines with Antiproliferative and Antitubulin Activity via Inverse Electron-Demand Diels-Alder Reaction of 1,2,4,5- Tetrazine#

Author(s): Olga I. Adaeva, Dmitry V. Demchuk, Roman A. Dolotov, Tatiana S. Kuptsova, Marina N. Semenova and Victor V. Semenov*

Volume 28, Issue 20, 2024

Published on: 03 July, 2024

Page: [1613 - 1620] Pages: 8

DOI: 10.2174/0113852728314401240613045216

Price: $65

Abstract

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.

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