This study aimed to investigate the relaxant effect of chroman compound HEF-04 on isolated vascular smooth muscle （VSM） and the possible underlying mechanisms involved. Isolated rabbit thoracic aorta was used as the...This study aimed to investigate the relaxant effect of chroman compound HEF-04 on isolated vascular smooth muscle （VSM） and the possible underlying mechanisms involved. Isolated rabbit thoracic aorta was used as the in vitro model and the relaxant effects of HEF-04 on endothelium-intact （＋EC） and endothelium-denuded （EC） thoracic aortic rings were compared. Potassium channel blockers, guanylate cyclase inhibitors, and COX-inhibitors were used to explore associations between the relaxant effects of HEF-04 with potassium channels, NO, and prostaglandin-like substances and endothelial hyperpolafizing factor （EDHF）, respectively. The results indicated that HEF-04 （1 × 10^-5 mol/L to 3× 10^-3 mol/L） had no significant impact on basal vascular tension, but could relax the contraction of vascular smooth muscle caused by high-K＋ solution in a dose-dependent manner. Indomethacin （5.6× 10^-6 mol/L） had no effect on vasorelaxation effect of HEF-04. In contrast, the vasorelaxant effect of HEF-04 was enhanced by methylene blue, which was significantly inhibited by calcium-dependent potassium channel blocker TEA. The vasorelaxant effect of HEF-04 on ＋EC thoracic aortic rings was significantly stronger than that on -EC thoracic aortic rings. The endothelium dependent relaxant effect of HEF-04 on VSM might be attributed to the interaction of HEF-04 with vascular relaxing factors or the increased release of EDHF.展开更多
Condensation of D-glucose, o-phenylenediamine and N,N-benzylphenylhydrazine hydrochloride (NNBPHH) in a one-pot reaction, or condensation of 2-(D-arabino-tetritol-1-yl) quinoxaline and NNBPHH, gave 3-(D-erythro-glycer...Condensation of D-glucose, o-phenylenediamine and N,N-benzylphenylhydrazine hydrochloride (NNBPHH) in a one-pot reaction, or condensation of 2-(D-arabino-tetritol-1-yl) quinoxaline and NNBPHH, gave 3-(D-erythro-glycerol-1- yl)-1-phenyl-1H-pyrazolo[3,4-b]quinoxaline. The structure of the latter was determined by 1H NMR spectroscopy and by synthesis using phenylhydrazine hydrochloride instead of NNBPHH. Condensation of D-glucose and 4,5-dichloro-o-phenylenediamine gave 6,7-dichloro-2-(D-arabino-tetritol-1-yl)quinoxaline, which upon condensation with NNBPHH gave the corresponding 6,7-dichloro-3-(D-erythro-glycerol-1-yl)-1-phenyl-1H-pyrazolo[3,4-b]quinoxaline. The structure and mechanism of formation of these compounds are discussed.展开更多
文摘This study aimed to investigate the relaxant effect of chroman compound HEF-04 on isolated vascular smooth muscle （VSM） and the possible underlying mechanisms involved. Isolated rabbit thoracic aorta was used as the in vitro model and the relaxant effects of HEF-04 on endothelium-intact （＋EC） and endothelium-denuded （EC） thoracic aortic rings were compared. Potassium channel blockers, guanylate cyclase inhibitors, and COX-inhibitors were used to explore associations between the relaxant effects of HEF-04 with potassium channels, NO, and prostaglandin-like substances and endothelial hyperpolafizing factor （EDHF）, respectively. The results indicated that HEF-04 （1 × 10^-5 mol/L to 3× 10^-3 mol/L） had no significant impact on basal vascular tension, but could relax the contraction of vascular smooth muscle caused by high-K＋ solution in a dose-dependent manner. Indomethacin （5.6× 10^-6 mol/L） had no effect on vasorelaxation effect of HEF-04. In contrast, the vasorelaxant effect of HEF-04 was enhanced by methylene blue, which was significantly inhibited by calcium-dependent potassium channel blocker TEA. The vasorelaxant effect of HEF-04 on ＋EC thoracic aortic rings was significantly stronger than that on -EC thoracic aortic rings. The endothelium dependent relaxant effect of HEF-04 on VSM might be attributed to the interaction of HEF-04 with vascular relaxing factors or the increased release of EDHF.
文摘Condensation of D-glucose, o-phenylenediamine and N,N-benzylphenylhydrazine hydrochloride (NNBPHH) in a one-pot reaction, or condensation of 2-(D-arabino-tetritol-1-yl) quinoxaline and NNBPHH, gave 3-(D-erythro-glycerol-1- yl)-1-phenyl-1H-pyrazolo[3,4-b]quinoxaline. The structure of the latter was determined by 1H NMR spectroscopy and by synthesis using phenylhydrazine hydrochloride instead of NNBPHH. Condensation of D-glucose and 4,5-dichloro-o-phenylenediamine gave 6,7-dichloro-2-(D-arabino-tetritol-1-yl)quinoxaline, which upon condensation with NNBPHH gave the corresponding 6,7-dichloro-3-(D-erythro-glycerol-1-yl)-1-phenyl-1H-pyrazolo[3,4-b]quinoxaline. The structure and mechanism of formation of these compounds are discussed.
