“Angular” Spirocyclic Azetidines: Synthesis, Characterization, and Evaluation in Drug Discovery
Alexander A. Kirichok, Hennadii Tkachuk, Kostiantyn Levchenko, Dmitry Granat, Tetyana Yegorova, Dmytro Lesyk, Anna Anisiforova, Yuliia Holota, Viktoriia Zomchak, Iryna Bodenchuk, Viktoriia Kosach, Petro Borysko, Rodion Korzh, Galeb Al-Maali, Vladimir Kubyshkin, Henry S. Rzepa, Pavel K. Mykhailiuk
Abstract
The previously neglected "angular" spirocyclic azetidines have been synthesized, characterized, and validated in drug discovery. We have shown that these compounds could act as bioisosteres for common saturated six-membered heterocycles. Their incorporation into the structure of the anticancer drug Sonidegib (instead of morpholine), and Danofloxacine (instead of piperazine) provided novel patent-free analogs with similar physicochemical properties and high activity.