Work

Synthesis of 3-(5-isopropyl-2,4-dimethoxyphenyl)-4-methoxybenzo[d]isoxazole-5-amine and its application for the preparation of new Hsp90 inhibitors

Year: 2025

Type: article

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.

Source: Proceedings of the National Academy of Sciences of Belarus Chemical Series

DOI: 10.29235/1561-8331-2025-61-3-218-226

Authors: N. A. Varabyeva, D. I. Paulovich, T. V. Chukarina, S. E. Ogurtsova, Y. A. Piven, F. A. Lakhvich

Institutions: National Academy of Sciences of Belarus, Institute of Bioorganic Chemistry

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: Belarusian Republican Foundation for Fundamental Research