Synthesis of 3-(5-isopropyl-2,4-dimethoxyphenyl)-4-methoxybenzo[d]isoxazole-5-amine and its application for the preparation of new Hsp90 inhibitors
https://doi.org/10.29235/1561-8331-2025-61-3-218-226
Abstract
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.
About the Authors
N. A. Varabyeva
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Varabyeva Nastassia A. – Postgraduate Student, Junior Researcher
5/2, Kuprevich Str., 220084, Minsk
D. I. Paulovich
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Paulovich Dzmitry I. – Master’s Student, Junior Researcher
5/2, Kuprevich Str., 220084, Minsk
T. V. Chukarina
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Chukarina Tatyana V. – Researcher. Institute of Bioorganic
5/2, Kuprevich Str., 220084, Minsk
S. E. Ogurtsova
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Ogurtsova Svetlana E. – Ph. D. (Biology), Head of the Department
5/2, Kuprevich Str., 220084, Minsk
Y. A. Piven
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Piven Yuri A. – Ph. D. (Chemistry), Associate Professor, Head of the Laboratory
5/2, Kuprevich Str., 220084, Minsk
F. A. Lakhvich
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Belarus
Belarus
Lakhvich Fedor A. – Academician, D. Sc. (Chemistry), Professor, Chief Researcher
5/2, Kuprevich Str., 220084, Minsk
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