Effective Synthesis of 3,4-Diaryl-isoxazole-5-carboxamides and their Antiproliferative Properties

Anna S. Maksimenko, Victor P. Kislyi, Natalia B. Chernysheva, Yuri A. Strelenko, Yan V. Zubavichus, Victor N. Khrustalev, Marina N. Semenova, Victor V. Semenov

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

A simple scalable procedure for the synthesis of 3,4-diaryl-isoxazole-5-carboxamides 6 under mild conditions from readily available material was developed. The targeted compounds 6, structural analogues of heat shock protein inhibitors, were obtained by the rearrangement of intermediate 3,4-diaryl-5-carboxamido-isoxazoline N-oxides 5. In contrast to carboxamido-isoxazoline oxides 5, base-catalyzed recyclization of 3,4-diaryl-5-(ethoxycarbonyl)isoxazoline N-oxides 9c unexpectedly yielded 5-hydroxy-1,2-oxazin-6-ones 17c instead of ethyl 3,4-diaryl-isoxazole-5-carboxylates 10. Crystal and molecular structure of 4-(2,5-dimethoxy-3,4-methylenedioxyphenyl)-5-hydroxy-3-phenyl-6H-1,2-oxazin-6-one 17c was established by single-crystal X-ray diffraction study. In a phenotypic sea urchin embryo assay, carboxamide 6f showed moderate antimitotic antitubulin activity compared to 5-unsubstituted 3,4-diarylisoxazoles 15, which featured strong microtubule destabilizing effect.

Original languageEnglish
Pages (from-to)4260-4270
Number of pages11
JournalEuropean Journal of Organic Chemistry
Volume2019
Issue number26
DOIs
Publication statusPublished - 14 Jul 2019
Externally publishedYes

Keywords

  • Antiproliferation
  • Nitrogen heterocycles
  • Recyclization
  • Urchin embryo

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