Synthesis and preliminary evaluation of anticonvulsant activity of some [4-(benzyloxy) benzoyl]- and [4-(benzyloxy) benzyl] aminoalkanol derivatives.
A variety of appropriate [4-(benzyloxy) benzoyl]- and [4-(benzyloxy) benzyl] aminoalkanol derivatives [I-XVII] was synthesized and evaluated for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (ScMet) tests in mice and rats. Neurotoxicity (TOX) was determined by the rotorod test. The most active compounds in the MES test in mice were the appropriate 4-(benzyloxy) benzyl derivatives of (R,S)- and S-(+)-2-amino-1-butanol [XI, XIII], 3-[4-(benzyloxy) benzyl] amino-3-methyl-1-butanol [XV], and S-(+)-2-[4-(benzyloxy) benzyl] amino-3-methyl-1-butanol [XVI]--all exhibiting 100% anti-MES protection (at 30 mg/kg, mice, i.p.) and non-toxic in the active doses. 4-[4-(Benzyloxy) benzyl] amino-1-butanol [X] exhibited activity in both MES and ScMet (100 mg/kg, mice, i.p., 100% anticonvulsant protection, 0.5 h and 4 h after administration, respectively).
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Medical College, Jagiellonian University, 9 Medyczna St., 30-688 Kraków, Poland.
Anna M
AM
Waszkielewicz
Marek
M
Cegła
Henryk
H
Marona
D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004597:Electroshock / Q000009:adverse effects / Q000379:methods; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology / Q000517:prevention & control
D000605:Amino Alcohols; D000927:Anticonvulsants; D010433:Pentylenetetrazole