Синтез 3-(5-изопропил-2,4-диметоксифенил)-4-метоксибензо[d]изоксазол-5-амина и его применение для получения новых ингибиторов Hsp90

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.

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