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

Effective Synthesis of 3,4‐Diaryl‐isoxazole‐5‐carboxamides and their Antiproliferative Properties Full article

Journal

European Journal of Organic Chemistry
ISSN: 1434-193X , E-ISSN: 1099-0690

Output data

Year: 2019, Volume: 2019, Number: 26, Pages: 4260-4270 Pages count : 11 DOI: 10.1002/ejoc.201900643

Authors

Maksimenko Anna S. ¹ , Kislyi Victor P. ¹ , Chernysheva Natalia B. ¹ , Strelenko Yuri A. ¹ , Zubavichus Yan V. ² , Khrustalev Victor N. ³ , Semenova Marina N. ⁴ , Semenov Victor V. ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry RAS,47 Leninsky Prospect, 119991, Moscow, Russian Federation
2	Russian Research Centre “Kurchatov Institute”; Kurchatov sq. 1 123182 Moscow Russian Federation
3	Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russian Federation
4	N. K. Koltzov Institute of Developmental Biology RAS, 26 Vavilov Street, 119334 Moscow, Russian Federation

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.

Maksimenko A.S. , Kislyi V.P. , Chernysheva N.B. , Strelenko Y.A. , Zubavichus Y.V. , Khrustalev V.N. , Semenova M.N. , Semenov V.V.
Effective Synthesis of 3,4‐Diaryl‐isoxazole‐5‐carboxamides and their Antiproliferative Properties
European Journal of Organic Chemistry. 2019. V.2019. N26. P.4260-4270. DOI: 10.1002/ejoc.201900643 WOS Scopus OpenAlex

Web of science:	WOS:000474190300001
Scopus:	2-s2.0-85068522401
OpenAlex:	W2953476189

DB	Citing
OpenAlex	19
Scopus	16
Web of science	15