ИСТИНА

Фундаментальной научной задачей проекта является исследование реакции нитрозирования гем-дигалогенциклопропанов с целью получения 5-хлор, 5-фтор и 5-бромизоксазолов, их галогенирование и функционализация путем введения фармакофорных фрагментов для получения потенциально биологически активных соединений, в том числе аналогов Комбретастатина А4 ряда изоксазола.

The isoxazole fragment is the basic scaffold of many biologically active compounds exhibiting antimicrobial, anti-inflammatory, anti-rheumatoid, anti-tumor and analgesic properties. A number of drugs used in medicine contain an isoxazole fragment as a subunit (Risperidone, Sulfafurazole, Valdecoxib, etc.). Over the past decades, isoxazoles have always been in the spotlight of medicinal chemistry. The project is aimed at the development of new approaches to the synthesis of substituted isoxazoles on the basis of gem-dihalocyclopropanes nitrosation. The reaction is characterized by high regioselectivity and affords good yields of 5-chloro-, 5-fluoro- and 5-bromoisoxazoles, valuable precursors for further modification of the isoxazole cycle, as well as nematicides. During the project implementation, they will be halogenated and functionalized by incorporating pharmacophore fragments to obtain compounds with potential biological activity. Synthesized haloisoxazoles will be introduced into cross-coupling reactions to create diverse libraries of functionalized isoxazoles including analogues of Combretastatin A4, an actively studied antitumor drug. The resulting compounds will be tested for antitumor and antibacterial activities. Based on the data obtained, leader compounds will be determined.