Synthesis and pharmacological evaluation of prodrugs of valproic acid.
We report the synthesis of (+/-)-3,6-Di-O-valproil-1,2:4,5-di-O-isopropylidene-myo-inositol (5) as well as (+/-)-3,6-Di-O-valproil-4,5-O-isopropylidene-myo-inositol (6) and (+/-)-3,6-Di-O-valproil-myo-inositol (7), which results from acid hydrolysis of the formers. The anticonvulsant activity of the compound 7 (MES test) expressed as ED50 is four times higher than that reported for valproic acid.
Bodor
N
N
Center for Drug Discovery, University of Florida, Gainesville, USA. bodor@cop.ufl.edu
Moon
S C
SC
Bruno-Blanch
L
L
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects; D004597:Electroshock; D007294:Inositol / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*
D000927:Anticonvulsants; D011355:Prodrugs; D007294:Inositol; D014635:Valproic Acid