Lipophilicity characterization of new N-phenylamino-azaspiranes as potential anticonvulsant agents.
The lipophilicity of a library of N-phenylamino-2-azaspiro[4.4]nonane- and [4.5]decane-1,3-dione derivatives has been determined by reversed-phase thin-layer chromatography with n-propanol-Tris buffer (pH 7.4) mixtures as mobile phases. Examination of chromatographic behaviour revealed a linear correlation between R(M) values and the concentration of n-propanol in the mobile phase. The partition coefficients (logP) were also calculated by use of the PrologP module of the Pallas computer program. Comparison of R(M0) values and calculated (logP(PALLAS)) data revealed the correlation expressed by the equation: logP(PALLAS) = 0.9995 R(M0) + 1.3451 (n = 28; r = 0.8971; F = 107.13; p < 0.05). The role of the lipophilicity in the anticonvulsant activity of a set of compounds examined is discussed: the active anticonvulsants were less lipophilic than inactive ones.
Obniska
Jolanta
J
Department of Pharmaceutical Chemistry, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland. mfobnisk@cyf-kr.edu.pl
Kamiński
Krzysztof
K
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D051381:Rats; D013141:Spiro Compounds / Q000737:chemistry*
D000927:Anticonvulsants; D008055:Lipids; D013141:Spiro Compounds; C099015:azaspirane