Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
J Med Chem ; 63(9): 4655-4684, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32118427

RESUMO

A high-throughput screen designed to discover new inhibitors of histone acetyltransferase KAT6A uncovered CTX-0124143 (1), a unique aryl acylsulfonohydrazide with an IC50 of 1.0 µM. Using this acylsulfonohydrazide as a template, we herein disclose the results of our extensive structure-activity relationship investigations, which resulted in the discovery of advanced compounds such as 55 and 80. These two compounds represent significant improvements on our recently reported prototypical lead WM-8014 (3) as they are not only equivalently potent as inhibitors of KAT6A but are less lipophilic and significantly more stable to microsomal degradation. Furthermore, during this process, we discovered a distinct structural subclass that contains key 2-fluorobenzenesulfonyl and phenylpyridine motifs, culminating in the discovery of WM-1119 (4). This compound is a highly potent KAT6A inhibitor (IC50 = 6.3 nM; KD = 0.002 µM), competes with Ac-CoA by binding to the Ac-CoA binding site, and has an oral bioavailability of 56% in rats.


Assuntos
Antineoplásicos/farmacologia , Histona Acetiltransferases/antagonistas & inibidores , Hidrazinas/farmacologia , Sulfonamidas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Descoberta de Drogas , Estabilidade de Medicamentos , Humanos , Hidrazinas/síntese química , Hidrazinas/química , Hidrazinas/farmacocinética , Masculino , Camundongos , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/metabolismo , Sulfonamidas/farmacocinética
2.
Phys Chem Chem Phys ; 14(29): 10119-21, 2012 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-22735595

RESUMO

We report on the use of protic ionic liquids, pILs, as solvents for the solubilisation and stabilization of viruses. We show that the shelf life of the pIL stabilized tobacco mosaic virus is significantly enhanced when compared to traditional phosphate buffer. This has new opportunities for the preparation, characterization and storage of viruses and virus based technologies.


Assuntos
Líquidos Iônicos/farmacologia , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Solanum lycopersicum/virologia , Folhas de Planta/virologia , Vírus do Mosaico do Tabaco/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA