Physicochemical characteristics of novel P-glycoprotein inhibitors of the cage dimeric 1,4-dihydropyridine type.
Physicochemical characteristics of two structurally different cage dimeric 1,4-dihydropyridines HX (1) and CC (2) have been determined and compared to their P-glycoprotein inhibiting properties. While the weakly basic compound (1) showed pH-dependent apparent partition coefficients (log D), the neutral compound (2) proved to have almost identical log D values at varying pH-values. The subsequent determination of partition coefficients (log P) resulted in comparably low log P values revealing a less lipophilic compound character. Determined significantly differing P-glycoprotein (P-gp) inhibitory properties indicated that the lipophilicity of the compounds does not play a decisive role for the P-gp activity.
Wollmann
J
J
Institute of Pharmaceutical Chemistry, Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany.
Molnár
J
J
Hilgeroth
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology*; D019281:Dimerization; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004095:Dihydropyridines; C038806:1,4-dihydropyridine