Synthesis of DL-fluorobenzenamides as anticonvulsants.
DL-2-Hydroxy-2-phenyl butyramide (1, CAS 52839-87-9), DL-3-hydroxy-3-phenyl pentanamide (2, CAS 131802-69-2) and DL-4-hydroxy-4-phenyl hexanamide (3, CAS 67880-30-2) are anticonvulsants. Searching for more active compounds, some DL-fluorobenzenamides were prepared and tested: DL-2-hydroxy-2-(3'-trifluoromethylphenyl)butyramide (4), DL-2-Hydroxy-2-4'-trifluoromethylphenyl) butyramide (5, CAS 620950-10-9), DL-2-hydroxy-2-[3',5'-bis(trifluoromethyl)phenyl]butyramide (6, CAS 620950-09-6), DL-3-hydroxy-3-(3'-trifluoromethylphenyl) pentanamide (7), DL-3-hydroxy-3-(4'-trifluoromethylphenyl)pentanamide (8), and DL-3-hydroxy-3-[3',5'-bis(trifluoromethyl)phenyl]pentanamide (9, CAS 863976-07-2). Compounds 4-9 exhibited anticonvulsant activity in seizures induced by pentylenetetrazol in mice. Incorporation of trifluoromethyl groups in the phenyl ring of 1, 2 and 3 increased their potency. Compounds 4, 6 and 9 exhibited a similar anticonvulsant activity as the reference drug phenobarbital (CAS 50-06-6).
Departamento de Bioqufmica, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, México. semeza@hotmail.com
Sergio Enrique
SE
Meza-Toledo
Fabiola
F
Lira-Zárate
Elsa Lizbeth
EL
Robles-Martínez
Belen
B
Peralta-Alvarez
Fabiola
F
Cabrera-Cedillo
Javier
J
Peralta-Cruz
Claudia
C
Cruz-Peinado
Humberto
H
Miñón-López
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D003292:Convulsants; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D010634:Phenobarbital / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D001549:Benzamides; D003292:Convulsants; D007202:Indicators and Reagents; D010433:Pentylenetetrazole; D010634:Phenobarbital