Synthesis and hypotensive activity of N-alkyl-N''-cyano-N'-pyridylguanidines

Abstract

A variety of N-alkyl-N''-pyridyl-N"-cyanoguanidines III were prepared as potential bioisosteres of hypotensive N-alkyl-N''-pyridylthioureas Ia. Optimal activity of the N,N''-disubstituted cyanoguanidines III was associated with the presence of 4-7 C-branched alkyl and 3- or 4-pyridyl groups. Maximum potency was displayed by N-tert-pentyl-N''-3-pyridyl-N"-cyanoguanidine (20). This compound was 200 times more potent than the corresponding thiourea in hypertensive rats and dogs. In comparison with guancydine, which is the de-3-pyridyl analog of 20, a 150-fold increase of potency in spontaneously hypertensive rats was obtained with 20 and its tert-butyl analog 19. The observed activity appears to be due to direct vascular relaxation. On a wt basis compounds 19, 20, 50 and 101 compared favorably with hydralazine.