5-Isoquinolinesulfonamide derivatives. 2. Synthesis and vasodilatory activity of N-(2-aminoethyl)-5-isoquinolinesulfonamide derivatives

Article abstract of DOI:10.1021/jm00121a010

A new series of aromatic sulfonamides, the N-(2-aminoethyl)-5-isoquinolinesulfonamide derivatives, 3, was synthesized from 5-isoquinolinesulfonic acid and shown to prossess vasodilatory action. Vasodilatory activity was evaluated in vivo in terms of increases in arterial blood flow in dogs after local injection in the femoral and/or vertebral arteries. When the alkylene group between the two nonaromatic nitrogen atoms was ethylene, the most potent activity was obtained. Alkylations of either of the two nonaromatic nitrogens yielded more active compounds, although bulky or excessively long alkyl groups reduced the potency. Among these derivatives, 27 and 47 were equipotent to diltiazem, which is used clinically as a cardiovascular drug. These two compounds also had antihypertensive and vasodilatory activities when administered intravenously, although the activities were less than that of diltiazem when given by this route.