A search for new antihypertensive agents. I. Alpha-adrenergic activity and selection of structures among pyrazine substituted imidazolines.

A group of new pyrazinylimidazolines was prepared and their effect on the contraction of isolated rat tail artery as well as their effect on blood pressure in urethane anesthetized normotensive rats were tested. The biological responses were compared to those elicited by standard imidazoline drugs and structure-activity relationships were analysed. The new chemical derivatives were subsequently synthetized and tested pharmacologically. Basing on the experimental results obtained and comparing these to the reported data on arylimidazolines the following suggestions have been put forward concerning the further modifications of alpha-adrenergically active pyrazinylimidazolines: 1) a distance of about 5 A should separate imidazoline nitrogen and pyrazine nucleus, 2) bond refractivity of the separating bridge should be above 5.33, 3) hydrophobicity of substituents in pyrazine ring must be possibly high.