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

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. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Authors
Maksimenko A.S.1 , Kislyi V.P.1 , Chernysheva N.B.1 , Strelenko Y.A.1 , Zubavichus Y.V. 2 , Khrustalev V.N. 3 , Semenova M.N.4 , Semenov V.V.1
Language
English
Status
Published
Year
2019
Organizations
  • 1 N. D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, Moscow, 119991, Russian Federation
  • 2 Russian Research Centre “Kurchatov Institute”, Kurchatov sq. 1, Moscow, 123182, Russian Federation
  • 3 Peoples' Friendship University of Russia (RUDN University), Moscow, 117198, Russian Federation
  • 4 N. K. Koltzov Institute of Developmental Biology RAS, 26 Vavilov Street, Moscow, 119334, Russian Federation
Keywords
Antiproliferation; Nitrogen heterocycles; Recyclization; Urchin embryo
Date of creation
19.07.2019
Date of change
19.07.2019
Short link
https://repository.rudn.ru/en/records/article/record/38814/
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