Synthesis and anticonvulsant properties of 3-(1,3,4-thiadiazol-2-yl) thiazolidin-4-ones.
A series of 2-substituted 3-(1,3,4-thiadiazol-2-yl)thiazolidin-4-ones were synthesized and evaluated for anticonvulsant activity in a genetic model of reflex epilepsy (sound-induced seizures in DBA/2 mice). The combination of preferred substituents in the 2-position coupled with the introduction of a mercapto group on the thiadiazole moiety led to a number of active compounds. The anticonvulsant activity of most derivatives is better than that of the clinically useful anticonvulsant sodium valproate and some of them appear to possess potencies in the same range as phenytoin and clobazam.
Chimirri
A
A
Dipartimento Farmaco-Chimico, Università di Messina, Italy.
Grasso
S
S
Monforte
A M
AM
Zappala
M
M
De Sarro
A
A
De Sarro
G B
GB
D000161:Acoustic Stimulation; D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000494:pharmacology; D000078306:Clobazam; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology; D013844:Thiazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D013830:Thiadiazoles; D013844:Thiazoles; D001569:Benzodiazepines; D000078306:Clobazam