Synthesis, vasodilating and antithrombotic activity of pyridyl-substituted silylisoxazolines

Abstract

3 - (2-Pyridyl) - 5 - phenyldimethylsilylisoxazoline, 3-(3-pyridyl) - 5 - phenyldimethylsilylisoxazoline and 3-(4-pyridyl) - 5 - phenyldimethylsilylisoxazoline were obtained by the [2+3] cycloaddition reaction of pyridyl nitrile oxides to phenyldimethylvinylsilane. The condensation of 3-pyridyl-substituted 5-triethoxysilylisoxazolines with triethanolamine afforded 3 - (2-pyridyl) - 5 - silatranylisoxazoline, 3 - (3 - pyridyl)-5-silatranylisoxazoline and 3-(4-pyridyl)-5-silatranylisoxazoline (12). In experiments in vivo and in vitro the vasodilating, antiarrhythmic and antithrombotic properties of pyridyl-substituted silylisoxazolines, their influence on the haemodynamic parameters in anaesthetized animals and their acute toxicity have been studied. It has been found that pyridyl-substituted silylisoxazolines possess vasodilating and antithrombotic properties. In experiments on the noradrenaline-preconstricted isolated rabbit ear artery, 3-(2-pyridyl)- and 3- (4- pyridyl) - 5 - phenyldimethylsilylisoxazoline exhibited pronounced vasodilating activity. 3 - (2 - Pyridyl) - and 3 - (3 - pyridyl) - 5 phenyldimethylsilylisoxazoline and 3-(2-pyridyl)-5-silatranylisoxazoline prolonged blood coagulation time