J. Knabe et al., RACEMATES AND ENANTIOMERS OF BASIC SUBSTI TUTED 5-PHENYLHYDANTOINS - SYNTHESES AND ANTIARRHYTHMIC ACTIVITY, Die Pharmazie, 52(12), 1997, pp. 912-919
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.