Cardioselective anti-ischemic ATP-sensitive potassium channel (KATP) openers: benzopyranyl indoline and indole analogues.
Eur J Med Chem
; 38(5): 459-71, 2003 May.
Article
em En
| MEDLINE
| ID: mdl-12767596
ABSTRACT
This paper describes the design, syntheses, and biological evaluations of novel ATP-sensitive potassium channel (K(ATP)) openers, benzopyranyl indoline and indole derivatives. Among those, two enantiomers of indoline-2-carboxylic ethyl esters (14, 18) showed the best cardioprotective activities both in vitro and in vivo, while their vasorelaxation potencies were very low (concentration for 50% inhibition of vasorelaxation >30 microM). The cardioprotective effect of 14 was completely reversed by 5-hydroxydecanoate, a selective mitochondrial K(ATP) blocker, indicating its provable protective mechanism through the mitochondrial K(ATP) opening. In addition, we performed conformational analyses using 2D-NMR, X-ray crystallography and molecular modeling to study the structure-activity relationships in this series of compounds.
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Bases de dados:
MEDLINE
Assunto principal:
Cardiotônicos
/
Canais de Potássio
/
Trifosfato de Adenosina
/
Isquemia Miocárdica
/
Indóis
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Coréia do Sul