2‐Aryl‐substituted 4H‐3,1‐benzoxazin‐4‐ones as novel active substances for the cardiovascular system

Abstract 4 H ‐3,1‐Benzoxazin‐4‐ones of the structural types 3 and 4 are accessible by cyclization reactions. The introduction of the phosphonate group was achieved by way of Wohl‐Ziegler bromination and subsequent Michaelis‐Arbuzow reaction with a trialkyl phosphite. Pharmacological investigations on isolated left atria, ileum specimens, and Langendorff hearts as well as in vivo circulatory studies on anesthetized rats revealed that the phosphonates 4 exert calcium antagonistic effects. Whereas 2‐(arylvinyl)benzoxazinones gave rise to pronounced negative inotropic effects, compound 3e exhibited relaxing effects on smooth musculature in particular and markedly increased the coronary flow through Langendorff hearts.