Synthesis and anticonvulsant evaluation of 1,2-diphenylethane derivatives, potential metabolites of denzimol.
A number of new 1,2-diphenylethane derivatives were synthesized and tested for anticonvulsant activity. Their structure was designed on the basis of the potential metabolic degradation of the imidazole ring present in denzimol ( ( +/- )-N-[2-[4-(beta-phenylethyl)phenyl]-2-hydroxethyl]imidazole), a potent anticonvulsant. The compounds which inhibited the electroshock-induced seizures (MES) in mice, namely N-[4-(beta-phenylethyl)phenacyl]formamide (VII) and N-[2-[4-(beta-phenylethyl)phenyl]-2-hydroxyethyl]formamide (IX), proved active also as inhibitors of the pentylenetetrazole-induced tonic seizures. The results of the pharmacological screening were evaluated in relation to the lipophilicity of the compounds.
Catto
A
A
Research Division, Recordati S.P.A., Milano.
Rossi
A
A
Leonardi
A
A
Testa
R
R
Nardi
D
D
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000378:metabolism; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D004597:Electroshock; D005260:Female; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D000927:Anticonvulsants; D007093:Imidazoles; C031307:denzimol; D010433:Pentylenetetrazole