[Stereoselective differences of central nervous system-depressive action of a homologous series of 3-alkyl-thalidomide analysis].
The racemates and the enantiomers of the 3-alkyl-thalidomide analogues 2a-c were synthesized via the lactams 1a-c. The absolute configuration of 1a-c and 2a-c was elucidated, their enantiomeric purity established. From racem. 2a 1,3-dimethylthalidomide (3) was synthesized. By means of the hexobarbital sleeping time prolongating effect in rats it was shown that racem. 2a and 3 were less CNS-depressant active than thalidomide; 3 caused a more prolonged sleeping time than 2a. Both enantiomers of 2a (i.p. 200 mg/kg) exceeded in their sleeping time prolongation action racem. 2a (same dose), whereby the (S)-enantiomer was to a factor of 1.8 more effective than the (R). With both enantiomers of 2a time and dose dependency of the effect were investigated. The enantiomers of 2b + c and 1a-c had also a prolongating effect on the hexobarbital sleeping time. Independently of the alkyl group the (S)-enantiomers were always more active than the respective (R)-enantiomers. (S)-1b (200 mg/kg) caused a long lasting loss of the righting reflexes as "own effect". Stereoselective differences between the enantiomers of 2a and 2b were observed only when a dose of 200 mg/kg was applied, whereas the higher activity of the (S)-enantiomers of 2c, 1b + c was obtained already with a lower dosage range.
Büch
H P
HP
Universität des Saarlandes, Fachrichtung Pharmakologie und Toxikologie, Homburg/Saar.
Omlor
G
G
Knabe
J
J
D000818:Animals; D002492:Central Nervous System Depressants / Q000138:chemical synthesis*; D005260:Female; D006591:Hexobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects; D013237:Stereoisomerism; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D002492:Central Nervous System Depressants; D013792:Thalidomide; D006591:Hexobarbital
Stereoselektive Unterschiede der zentralnervös-depressorischen Wirkung in einer homologen Reihe von 3-Alkyl-Thalidomid-Analoga.