ChemInform Abstract: Synthesis and Bradycardic Activity of a Series of Substituted 3- Aminoalkyl-2,3-dihydro-4H-1,3-benzoxazin-4-ones as Potent Antiischemics

A series of 2,3-dihydro-4 H -1,3-benzoxazin-4-ones substituted at the 3-position with an arylalkyaminoalkyl group have been synthesized and their specific bradycardic and antiarrythmic activities evaluated. Bradycardia is optimal when the aromatic rings are substituted with methoxy groups and the side-chain amine is N -methylated. N -Demethylated and 2-alkylated derivatives show the highest antiarrhythmic activity but have little bradycardic action. Most of the compounds described are more potent than Falipamil. Compound 1m (F 3226) has been selected for further pharmacological tests and the bradycardic activity has been confirmed when administered orally to anesthetized rats without notable side effects.