An Old Story in the Parallel Synthesis World: An Approach to Hydantoin Libraries.
ACS Comb Sci
; 20(1): 35-43, 2018 01 08.
Article
en En
| MEDLINE
| ID: mdl-29227678
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Aurora Quinasa A
/
Hidantoínas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
ACS Comb Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
Ucrania