Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores
We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carri...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2006
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| Sorozat: | BIOORGANIC & MEDICINAL CHEMISTRY
14 No. 19 |
| Tárgyszavak: | |
| doi: | 10.1016/j.bmc.2006.05.065 |
| mtmt: | 1132576 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/22861 |
| Tartalmi kivonat: | We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carried out on isolated rat heart preparations using the non-recirculating Langendorff mode. The new analogues were present, at 10 mu M concentration, during ischemia and reperfusion. Selected compounds were further studied by a conventional microelectrode method in order to get insight into their cellular mode of action. The most active compound, N-[4-[2-[[2-(3,4-dihydro-6-hydroxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5 -yl)ethyl] methylamine]ethyl]phenyl]methanesulfonamide (19a), reduces premature beats, prolongs QT and QRS intervals during ischemia and reperfusion, and reduces MDA content, leading to a fast recovery of the heart. In addition, it exhibits moderate class III antiarrhythmic action. (c) 2006 Elsevier Ltd. All rights reserved. |
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| Terjedelem/Fizikai jellemzők: | 6666-6678 |
| ISSN: | 0968-0896 |