Synthesis, Vasodilating, Antithrombotic and Cardioprotective Activity of Pyridyl Substituted 5-Silyl(Germyl)Isoxazolines-2

The reactions of [2+3] cycloaddition of pyridylnitrile oxides to vinyl- and allylgermanes proceed regioselectively and afford 5-Ge-substituted isoxazolines-2. We have synthesized 9 new pyridyl substituted 5-Si(Ge)-isoxazolines-2 and investigated their biological activity. The vasodilating, anticoagulant and cardioprotective activities of 5-Si(Ge) substituted isoxazolines-2 have been studied in vitro and in vivo. Substitution of the silicon atom for the germanium one leads to the significant increase in vasodilating, antithrombotic and cardioprotective activity. The insertion of the methylene group between Ge and the isoxazoline ring reduces the vasodilating activity. The most active isoxazoline - 3-(5‵-triethylgermyl-3‵-isoxazolinyl)pyridine hydrochloride protects the heart from rhythm disturbances and lethality during ischaemia-reperfusion.