Document Report Card

ID: ALA1124108

Journal: J Med Chem

Title: Antihypertensive thiadiazoles. 2. Vasodilator activity of some 2-aryl-5-guanidino-1,3,4-thiadiazoles.

Authors: Turner S, Myers M, Gadie B, Hale SA, Horsley A, Nelson AJ, Pape R, Saville JF, Doxey JC, Berridge TL.

Abstract: Some 2-aryl-5-guanidino-(or N-substituted guanidino)-1,3,4-thiadiazoles and closely related analogues were found to lower blood pressure in metacorticoid (DOCA) hypertensive rats. In the unsubstituted guanidines that exhibited low toxicity, optimum activity resulted when the aryl group was a 2-methylphenyl ring (11). Modifications to the guanidine group did not increase antihypertensive activity, but, in the 2-methylphenyl series, the N-n-butyl- and N-(2-methoxyethyl)guanidines (63 and 78) and the related iminoimidazolidine 93 were of comparable activity to that of the unsubstituted guanidine 11. The iminoimidazolidine 93 showed a somewhat longer duration of action than the guanidine derivatives. Preliminary studies in a pithed rat preparation indicated that these thiadiazole derivatives (11, 63, and 93) lowered blood pressure by a direct relaxant effect on vascular smooth muscle.

CiteXplore: 3361579

DOI: 10.1021/jm00400a004