Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH or 2-CH.

A series of twenty two (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH or 2-CH was designed, synthesized and evaluated for anticonvulsant activity in rodent models of seizures: maximal electroshock (MES) test, subcutaneous pentylenetetrazole (scPTZ) test, and 6-Hz test. There were identified three most active compounds: S-(2E)-N-(1-hydroxypropan-2-yl)-3-(2-methylphenyl)prop-2-enamide (5) (ED MES=42.56, ED scPTZ=58.38, ED 6-Hz 44mA=42.27mg/kg tested in mice after intraperitoneal (i.p.) administration); R,S-(2E)-3-(4-chlorophenyl)-N-(1-hydroxybutan-2-yl)prop-2-enamide (6) (ED MES=53.76, ED scPTZ=90.31, ED 6-Hz 44mA=92.86mg/kg mice, i.p.); and R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide (11) (ED MES=55.58, ED scPTZ=102.15, ED 6-Hz 44mA=51.27mg/kg mice, i.p.). Their structures and configurations were confirmed by crystal X-ray diffraction method. The structure-activity studies among the tested series showed that chlorine atom in position para or methyl group in position ortho of phenyl ring were beneficial for anticonvulsant activity. Methyl group in position para of phenyl ring decreased anticonvulsant activity in reported series of cinnamamide derivatives.