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Cardioselective anti-ischemic ATP-sensitive potassium channel (KATP) openers: benzopyranyl indoline and indole analogues
- Source :
-
European Journal of Medicinal Chemistry . May2003, Vol. 38 Issue 5, p459. 13p. - Publication Year :
- 2003
-
Abstract
- This paper describes the design, syntheses, and biological evaluations of novel ATP-sensitive potassium channel (KATP) 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 μM). The cardioprotective effect of 14 was completely reversed by 5-hydroxydecanoate, a selective mitochondrial KATP blocker, indicating its provable protective mechanism through the mitochondrial KATP 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 02235234
- Volume :
- 38
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- European Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 9857265
- Full Text :
- https://doi.org/10.1016/S0223-5234(03)00063-1