Synthesis and structure activity relationship of fluorinated enaminones: Potential antiepileptic compunds
A series of fluorinated enaminones have been synthesized from the condensation of 5-(trifluoromethyl)-1,3-cyclohexanedione and various amines via the synergistic effect of p-toluenesulfonic acid/acetic acid. The activity of 3-(4-chlorophenylamino)-5-(trifluoromethyl)cyclohex-2-enone (ADD 386002) and 3-(benzylamino)-5-(trifluoromethyl)cyclohex-2-enone (ADD 386001) have been established by our research group as lead compounds with significant anticonvulsant activity in the maximal electroshock (MES) seizure test model. The synthesis of these enaminones will help to advance the chemistry of these compounds as well as provide insight to their structural activity relationships, as potential antiepileptic agents. Using the above procedure, we completed the synthesis of fourteen new fluorinated enaminones containing substituted phenyl and heteroaromatic rings. All 14 compounds were characterized by NMR and GC/MS. The lipophilicity of each compound was calculated in order to determine the membrane permeability. All the compounds showed acceptable logP values. Seven compounds are currently undergoing testing at the Antiepiletic Drug Screening branch of NINDS.
Pharmacy sciences|Physical chemistry
Okoromoba A.E Otome,
"Synthesis and structure activity relationship of fluorinated enaminones: Potential antiepileptic compunds"
ETD Collection for Tennessee State University.