Conformational analogues of antihypertensive agents related to guanethidine

In an effort to clarify the conformational requirements, if any, of agents producing adrenergic neuronal blockade through mechanisms similar to guanethidine, the synthesis and pharmacological evaluation of 15 analogues of cinnamylguanidine are described. These analogues represent derivatives in which the distance between the center of the ring system and the guanidinium nitrogen atom varies from 3.9 to 6.2 A. While conformational relationships could not be defined in this study, three analogues (3, 4, and 5) were apparently more potent than guanethidine in the in vitro assay employed.