RACEMATES AND ENANTIOMERS OF BASIC SUBSTI TUTED 5-PHENYLHYDANTOINS - SYNTHESES AND ANTIARRHYTHMIC ACTIVITY

The racemates and the enantiomers of 5-phenylhydantoins with basic sub stituents in 5-position are synthesized on two different routes via th e Bucherer-Bergs-reaction. Using lanthanide-shift-reagents the enantio meric excess for the enantiomers of 3-methyl-5-morpholinomethyl-5-phen ylhydantion (3a) and 3-methyl-5-phenyl-5-(2-phthalimidoethyl) (6a) is found to be more than 98%. The enantiomers of 4d, 5b, 6b, 7a and 7b, d erived from 3a and 6a, possess the same optical purity. The racemates and the enantiomers of 3a, 4d and 5b were tested at atrium of rat hear ts on their antiarrhythmic activity. At the right atrium (+)-3a, (+)-4 d, and (+)-5b reduce the spontaneous frequence dependent on the dosis. At the left atrium the enantiomers of 3a and 4d show a negative inotr opic action (+)-3a is 4.1, (+)-4d is 1.5 more active as the correspond ing (-)-enantiomers. Compound (+)-4d exceeds the reference substance d iphenylhydantoin by the factor 1.3.