2-Ethynylbenzenealkanamines: a new class of calcium entry blockers with potential antihypertensive and antianginal properties

2-Ethynylbenzenealkanamines represent a newly discovered class of calcium channel blockers in that they inhibited KCl-stimulated /sup 45/Ca influx and isometric tension development in isolated vascular smooth muscle and prolonged AV-nodal conduction time in canine hearts. Testing revealed optimal activity in the following structure where R1 is aryl, R2 and R4 are methyl, R3 is aralkyl and X is methoxy: compounds in this group lowered arterial pressures in conscious spontaneously hypertensive rats and renal hypertensive dogs following either oral or parenteral administration, and thus are potential antihypertensive agents. These compounds also caused coronary vasodilation at concentrations which did not affect rate or force of contraction in the isolated, perfused guinea pig heart preparation, they increased coronary blood flow and decreased coronary vascular resistance in the anesthetized canine, and thus are potential antianginal agents. In summary, 2-ethynylbenzenealkanamines represent a new class of calcium entry blockers which have potential antihypertensive and antianginal properties.