title: Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3or 2-CH3.
abstract: A series of twenty two (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3or 2-CH3was 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) (ED50MES=42.56, ED50scPTZ=58.38, ED506-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) (ED50MES=53.76, ED50scPTZ=90.31, ED506-Hz 44mA=92.86mg/kg mice, i.p.); and R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide (11) (ED50MES=55.58, ED50scPTZ=102.15, ED506-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.
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland. Electronic address: agnieszka.gunia@uj.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gunia-Krzyżak
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Żelaszczyk
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Rapacz
authors.affiliation: Department of Chemistry, Institute of Biology, Pedagogical University, Podchorążych 2, 30-084 Krakow, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Żesławska
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Waszkielewicz
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pańczyk
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Słoczyńska
authors.affiliation: Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Pękala
authors.affiliation: Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Nitek
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Marona
mesh_terms: D000605:Amino Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D000605:Amino Alcohols; D000927:Anticonvulsants
keywords: 6-Hz; Anticonvulsant; Cinnamamide; Crystal structure; MES; Pharmacophore; scPTZ