| Autor: |
Bogolubsky AV; Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine., Moroz YS; Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine.; National Taras Shevchenko University of Kyiv , 60 Volodymyrska Street, Kyiv 01601, Ukraine., Savych O; Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine.; National Taras Shevchenko University of Kyiv , 60 Volodymyrska Street, Kyiv 01601, Ukraine., Pipko S; Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine.; National Taras Shevchenko University of Kyiv , 60 Volodymyrska Street, Kyiv 01601, Ukraine., Konovets A; Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine.; National Taras Shevchenko University of Kyiv , 60 Volodymyrska Street, Kyiv 01601, Ukraine., Platonov MO; Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine., Vasylchenko OV; Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine., Hurmach VV; Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine.; National Taras Shevchenko University of Kyiv , 60 Volodymyrska Street, Kyiv 01601, Ukraine., Grygorenko OO; Enamine Ltd. , 78 Chervonotkatska Street, Kyiv 02094, Ukraine.; National Taras Shevchenko University of Kyiv , 60 Volodymyrska Street, Kyiv 01601, Ukraine. |
| Abstrakt: |
An approach to the parallel synthesis of hydantoin libraries by reaction of in situ generated 2,2,2-trifluoroethylcarbamates and α-amino esters was developed. To demonstrate utility of the method, a library of 1158 hydantoins designed according to the lead-likeness criteria (MW 200-350, cLogP 1-3) was prepared. The success rate of the method was analyzed as a function of physicochemical parameters of the products, and it was found that the method can be considered as a tool for lead-oriented synthesis. A hydantoin-bearing submicromolar primary hit acting as an Aurora kinase A inhibitor was discovered with a combination of rational design, parallel synthesis using the procedures developed, in silico and in vitro screenings. |
