Synthesis of N4-(2,4-dimethylphenyl) semicarbazones as 4-aminobutyrate aminotransferase inhibitors.
Several 2,4-dimethylphenyl substituted semicarbazones were synthesized in three steps involving aryl urea and aryl semicarbazide formation. The structures were confirmed by spectral and elemental analyses. All the compounds were evaluated for anticonvulsant activity by using a series of test models, including maximal electroshock seizure, subcutaneous pentylenetetrazole and subcutaneous strychnine seizure threshold tests. The compounds were also evaluated for behavioural impairement and depression activity. In the neurochemical investigation, potent compounds were evaluated for their effects on rat brain gamma-aminobutyric acid (GABA) levels and in vitro gamma-aminobutyrate transaminase (Pseudomonas fluorescens) activity. Preliminary studies suggest that these compounds exhibit anticonvulsant activity via a GABA-mediated mechanism.
Yogeeswari
Perumal
P
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani-333031, India. pyogee@bits-pilani.ac.in
Sriram
Dharmarajan
D
Thirumurugan
Rathinasabapathy
R
Jeewanlal
Logantha Ramamoorthy
LR
Jit
Sunil
S
Ragavendran
Jegadeesan Vaigunda
JV
Kavya
Ramkumar
R
Rakhra
Kavya
K
Saraswat
Vivek
V
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy*; D012664:Semicarbazones / Q000138:chemical synthesis / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D000927:Anticonvulsants; D012664:Semicarbazones; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase