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

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

Volume: 28 Issue: 20

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

Affiliation:

• N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prospect, Moscow, 119991, Russian Federation

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.

Cite this article as:

Adaeva I. Olga, Demchuk V. Dmitry, Dolotov A. Roman, Kuptsova S. Tatiana, Semenova N. Marina and Semenov V. Victor*, Synthesis of Polyoxygenated 4,5-Diarylpyridazines with Antiproliferative and Antitubulin Activity via Inverse Electron-Demand Diels-Alder Reaction of 1,2,4,5- Tetrazine#, Current Organic Chemistry 2024; 28 (20) . https://dx.doi.org/10.2174/0113852728314401240613045216