3,4-Methylenedioxyphenyl-, isopropylidenedioxyphenyl-, and benzyl-substituted chiral 2-aminosuccinimides and 3-aminopyrrolidines. Stereoselective investigations of potential anti-parkinsonian, antipsychotic, and anticonvulsant activities.
The chiral title compounds 2--11 were assessed for their potential anti-Parkinsonian, antipsychotic, and anticonvulsant properties. The most striking differences in the biological activity of enantiomeric pairs were noted for D-(R)-2-amino-N-(3,4-methylenedioxyphenyl)succinimide hydrochloride (2) vs. L-(S)-3 and D-(R)-2-amino-N-(3,4-isopropylidenedioxyphenyl)succinimide (4) vs. L-(S)-5. D-(R)-2-partially attenuated amphetamine-induced stereotyped behavior, whereas D-(R)-4 antagonized oxotremorine-induced tremors. Their respective enantiomorphs were inactive in these tests. No differences in anticonvulsant potency of enantiomeric pairs were observed. The stereoselective actions of D-(R)-2 and 4 were rationalized on the basis of the presence or absence of gem-dimethyl functions in isopropylidenedioxy vs. methylenedioxy groups; the data seem to indicate that these methyl groups influence selective receptor site interaction in the D-(R) series.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis*; D000978:Antiparkinson Agents / Q000138:chemical synthesis*; D014150:Antipsychotic Agents / Q000138:chemical synthesis*; D006801:Humans; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D011759:Pyrrolidines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000517:prevention & control; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects; D013388:Succinimides / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology
D000927:Anticonvulsants; D000978:Antiparkinson Agents; D014150:Antipsychotic Agents; D011759:Pyrrolidines; D013388:Succinimides