Quantitative structure-anticonvulsant activity relationships of valproic acid, related carboxylic acids and tetrazoles

摘要: Valproic acid and several structurally related carboxylic acids tetrazole analogues have been shown to antagonize seizures induced by pentylenetetrazole in mice. To investigate the influence of alkyl substituents on anticonvulsant activity, octanol-water partition coefficients relative pKa values were determined. Within series active acids, there was a good correlation between activity coefficient (r = 0.86). The small but statistical significance. When most compound, 5-heptyltetrazole added series, low linear combination lipophilicity resulted. effect polar moieties alkyl-substituted compounds assessed comparison regression equations with either an or dipole moment term for lipophilicity. It appears that other factors, such as nature substituent, activity. inactivity cyclohexylmethyl-substituted compounds, cyclohexylacetic 5-cyclohexylmethyltetrazole may be due subtle steric effects at critical step, involving oxidative metabolism interaction site.