The study of the lipophilicity of some aminoalkanol derivatives with anticonvulsant activity.
A series of new (phenoxyethyl)aminoalkanol derivatives were synthesized and evaluated for their anticonvulsant activity. The most promising compound seemed to be (R,S)-1N-[(2,6-dimethyl)phenoxyethyl]amino-2-butanol, which displayed anti-MES activity (in mice, i.p.) with protective index (TD(50) /ED(50) ) of 5.712, corresponding to that of phenytoin (6.6), carbamazepine (4.9) and valproate (1.7). The lipophilicity of compounds 1-17 exhibiting anticonvulsant activity was investigated. Their lipophilicities (R(M0) ) were determined using reversed-phase thin-layer chromatography (RP-TLC) with a mixture of acetone and water as mobile phases. The partition coefficients of 1-17 (logP) were also calculated using two computer programs (Pallas and ALOGPS) and compared with R(M0) . The relationship between anticonvulsant activity and lipophilicity of the tested substances was estimated.
Waszkielewicz
Anna
A
Department of Bioorganic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Str, 30-688 Cracow, Poland.
Szkaradek
Natalia
N
Pękala
Elżbieta
E
Galzarano
Fabiola
F
Marona
Henryk
H
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D002220:Carbamazepine / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D056148:Chromatography, Reverse-Phase / Q000295:instrumentation / Q000379:methods*; D002855:Chromatography, Thin Layer / Q000295:instrumentation / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D008055:Lipids / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D012995:Solubility; D014635:Valproic Acid / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry
D000927:Anticonvulsants; D008055:Lipids; D002220:Carbamazepine; D014635:Valproic Acid