vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8331-2025-61-3-218-226vestich-967Research ArticleБИООРГАНИЧЕСКАЯ ХИМИЯBIOORGANIC CHEMISTRYСинтез 3-(5-изопропил-2,4-диметоксифенил)-4-метоксибензо[d]изоксазол-5-амина и его применение для получения новых ингибиторов Hsp90Synthesis of 3-(5-isopropyl-2,4-dimethoxyphenyl)-4-methoxybenzo[d]isoxazole-5-amine and its application for the preparation of new Hsp90 inhibitorsВоробьеваА. О.VarabyevaN. A.

Воробьева Анастасия Олеговна – аспирант, младший научный сотрудник

ул. Купревича, 5/2, 220084, Минск

Varabyeva Nastassia A. – Postgraduate Student, Junior Researcher

5/2, Kuprevich  Str.,  220084,  Minsk

varabyevana@iboch.byПавловичД. И.PaulovichD. I.

Павлович Дмитрий Игоревич – магистрант, младший научный сотрудник

ул. Купревича, 5/2, 220084, Минск

Paulovich Dzmitry I. – Master’s Student, Junior Researcher

5/2, Kuprevich  Str.,  220084,  Minsk

dimapavlovich@gmail.comЧукаринаТ. B.ChukarinaT. V.

Чукарина Татьяна Владимировна – научный сотрудник

ул. Купревича, 5/2, 220084, Минск

Chukarina Tatyana V. – Researcher. Institute of Bioorganic

5/2, Kuprevich  Str.,  220084,  Minsk

chukagirl@gmail.comОгурцоваС. Э.OgurtsovaS. E.

Огурцова Светлана Эдуардовна – кандидат биологических наук, заведующий отделом

ул. Купревича, 5/2, 220084, Минск

Ogurtsova Svetlana E. – Ph. D. (Biology), Head of the Department

5/2, Kuprevich  Str.,  220084,  Minsk

s.ogurtsova@iboch.byПивеньЮ. А.PivenY. A.

Пивень Юрий Андреевич – кандидат химических наук, доцент, заведующий лабораторией

ул. Купревича, 5/2, 220084, Минск

Piven Yuri A. – Ph. D. (Chemistry), Associate Professor, Head of the Laboratory

5/2, Kuprevich  Str.,  220084,  Minsk

piven.ya@gmail.comЛахвичФ. А.LakhvichF. A.

Лахвич Федор Адамович – академик, доктор химических наук, профессор, главный научный сотрудник

ул. Купревича, 5/2, 220084, Минск

Lakhvich Fedor A. – Academician, D. Sc. (Chemistry), Professor, Chief Researcher

5/2, Kuprevich  Str.,  220084,  Minsk

lakhvich@iboch.byИнститут биоорганической химии Национальной академии наук БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of Belarus202529082025613218226Copyright © Воробьева А.О., Павлович Д.И., Чукарина Т.B., Огурцова С.Э., Пивень Ю.А., Лахвич Ф.А., 20252025Воробьева А.О., Павлович Д.И., Чукарина Т.B., Огурцова С.Э., Пивень Ю.А., Лахвич Ф.А.Varabyeva N.A., Paulovich D.I., Chukarina T.V., Ogurtsova S.E., Piven Y.A., Lakhvich F.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/967

Основываясь на 3-(5-изопропил-2,4-диметоксифенил)-6,7-дигидробензо[d]изоксазол-4(5H)-оне – скаффолде для получения новых ингибиторов Hsp90, разработана эффективная схема синтеза 5-амино-4-метоксибензо[d]изоксазолов.  Ключевыми  стадиями  в  синтезе  были  дибромирование  в  положение  5,  ароматизация и последующее медькатализируемое кросс-сочетание 5-бром-4-метоксибензо[d]изоксазола с азидом натрия с одновременным восстановлением до 5-амино-4-метоксибензо[d]изоксазола. С использованием разработанной схемы получен потенциальный ингибитор Hsp90, который проявил высокую антипролиферативную активность в отношении клеток рака молочной железы линий ВТ-474 (IC50 = 5 мкM) и умеренную активность в отношении клеток линии MCF-7.

An efficient synthetic scheme for 5-amino-4-methoxybenzo[d]isoxazoles has been developed starting from 3-(5-isopropyl-2,4-dimethoxyphenyl)-6,7-dihydrobenzo[d]isoxazole-4(5H)-one – a scaffold for the preparation of new Hsp90 inhibitors. The key stages in the synthesis included dibromination at position 5, aromatization, and subsequent copper-catalyzed cross-coupling of 5-bromo-4-methoxybenzo[d]isoxazole with sodium azide, with simultaneous reduction to 5-amino-4-methoxybenzo[d]isoxazole. Using the developed scheme, a potential Hsp90 inhibitor was obtained, which showed high antiproliferative activity against breast cancer cells of BT-474 line (IC50 = 5 µM) and moderate activity against MCF-7 cells.

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The authors declare that there are no conflicts of interest present.