An Old Story in the Parallel Synthesis World: An Approach to Hydantoin Libraries

• DOI: 10.1021/acscombsci.7b00163
• Publication Date: 2017-12-11T23:36:54Z
• Authors: Andrey V. Bogolubsky; Yurii S. Moroz; Olena Savych; Sergey Pipko; Angelika Konovets; Maxim O. Platonov; Oleksandr V. Vasy...; Vasyl V. Hurmach; Oleksandr O. Gryg...
• Keywords: Hydantoin; Lead compound

An approach to the parallel synthesis of hydantoin libraries by reaction in situ generated 2,2,2-trifluoroethylcarbamates and α-amino esters was developed. To demonstrate utility method, a library 1158 hydantoins designed according lead-likeness criteria (MW 200-350, cLogP 1-3) prepared. The success rate method analyzed as function physicochemical parameters products, it found that can be considered tool for lead-oriented synthesis. A hydantoin-bearing submicromolar primary hit acting an Aurora kinase inhibitor discovered with combination rational design, using procedures developed, silico vitro screenings.