RESUMO
The design and synthesis of a new series of c-Jun N-terminal kinase-3 (JNK3) inhibitors with selectivity against JNK1 are reported. The novel series of substituted 2'-anilino-4,4'-bipyridines were designed based on a combination of hits from high throughput screening and X-ray crystal structure information of compounds crystallized into the JNK3 ATP binding active site.
Assuntos
Compostos de Anilina/química , Desenho de Fármacos , Proteína Quinase 10 Ativada por Mitógeno/antagonistas & inibidores , Piridinas/síntese química , Piridinas/farmacologia , Animais , Cristalografia por Raios X , Concentração Inibidora 50 , Proteína Quinase 10 Ativada por Mitógeno/química , Proteína Quinase 10 Ativada por Mitógeno/metabolismo , Modelos Moleculares , Estrutura Terciária de Proteína , Piridinas/química , Ratos , Relação Estrutura-AtividadeRESUMO
The base-mediated rearrangement of epoxides into allylic alcohols is a well-known synthetic transformation. The first enantioselective version of the reaction using a chiral base was reported in 1980. Since then, the reaction has received a lot of attention mostly due to the great usefulness of chiral allylic alcohols in organic synthesis. Major breakthroughs in the area were the first report on using a sub-stoichiometric amount of chiral base, and the development of chiral bases for a true catalytic reaction protocol. The present review covers the time from when the first asymmetric epoxide isomerisation reaction was reported (1980) up to now, focusing on the period 1997-2001.